New therapy extends breast cancer survival rate, prevents reoccurrence

Vaccine to treat and prevent lung, bowel and pancreatic cancer shows promise in the lab

  • October 22, 2020

An experimental vaccine, designed to enlist the body’s own immune system to target cancer cells, has shown promise for treating and preventing cancer in mice.

The vaccine was created to target a gene called KRAS that is involved in the development of many types of cancer, including lung, bowel and pancreatic cancer.

Researchers from the same team have also found a new way to spot and treat aggressive forms of lung cancers that are able to evade the body’s immune system.

Both studies will be presented on Sunday at the 32nd EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics, which is taking place online.

Scientists have known for decades that the KRAS gene goes wrong – or mutates – in many cancers. However, until now, researchers have struggled to find a way to turn this knowledge into an effective treatment.

The vaccine study [2] was carried out by Dr Rachel Ambler, a postdoctoral research fellow, and colleagues at The Francis Crick Institute, London, UK. She said: “We know that if KRAS goes wrong, it enables cells in our bodies to start multiplying and turning into cancer cells. Recently, we’ve learned that, with the right help, the body’s immune system might be capable of slowing this growth.

“We wanted to see if we could use this knowledge to create a cancer vaccine that could not only be used to treat cancer, but also give long-lasting protection against cancer, with minimal side-effects.”

Dr Ambler and her colleagues created a set of vaccines that are capable of stimulating an immune response towards the most common KRAS mutations.

The vaccines are made up of two elements joined together. One element is a fragment of the protein produced by cancer cells with a mutated KRAS gene. The other element is an antibody that helps to deliver the vaccine to a cell of the immune system called a dendritic cell. These cells play a key role in helping the immune system spot and destroy cancer cells, an ability that could be boosted by the vaccines.

The team tested the vaccine on mice that already had lung tumours and mice that were induced to grow tumours. Researchers studied the mice for indications that their immune systems were responding to the vaccine and for signs that tumours were shrinking or not even forming in the first place.

In mice with tumours, 65% of those treated with the vaccine were alive after 75 days, compared to 15% of mice that were not given the vaccine.

In mice treated to induce tumours, 40% of vaccinated mice remained tumour-free after 150 days, compared to only 5% of unvaccinated mice (one mouse). By vaccinating the mice, researchers found that the appearance of tumours was delayed by an average of around 40 days.

Dr Ambler said: “When we used the vaccine as a treatment, we found that it slowed the growth of cancers in the mice. And when we used it as a preventative measure, we found that no cancers grew in the mice for quite a long period of time and, in many cases, cancers never developed.

“Previous trials of cancer vaccines have failed because they have not been able to create a strong enough response from the immune system to find and destroy cancer cells. This research still has a long way to go before it could help prevent and treat cancer in people, but our results suggest that the design of this vaccine has created a strong response in mice with very few side-effects.”

Researchers from the same team have also made an important discovery about how lung cancers are able to evade the body’s immune system, making them harder to treat. Their findings will be discussed in two further presentations at the 32th EORTC-NCI-AACR Symposium. [3,4]

Dr Sophie de Carné, a postdoctoral researcher, and Dr Phil East, deputy head of bioinformatics, from The Francis Crick Institute used a collection of hundreds of human tumour samples with information on which genes are mutated and which genes are active inside the tumours. They were also interested in the KRAS gene and its role in the development of hard-to-treat cancers.

Dr de Carné said: “In patients with some of the most aggressive cancers, we discovered that the activity of the KRAS gene results in the build up of a chemical called adenosine. Higher levels of adenosine are known to dampen the body’s immune response, making it harder for immune cells to target and destroy cancer cells.”

The researchers then studied cancers with similar KRAS activity in mice to see whether it was possible to manipulate the levels of adenosine to make it easier to treat the cancer. By giving the mice a drug designed to lower adenosine, oleclumab made by AstraZeneca, alongside existing cancer drugs that help the immune system fight cancer, the researchers found that they could improve survival.

Dr East added: “Together these results suggest it could eventually be possible to identify patients who have this aggressive type of lung cancer and use a combination of drugs to support their immune system and successfully treat their tumours.”

Dr James L. Gulley is co-chair of the 32th EORTC-NCI-AACR Symposium for the NCI and Director of the Medical Oncology Service, Center for Cancer Research, NCI, USA, and was not involved in the research. He said: “These studies focus on types of cancer – such as lung and pancreatic cancer – that are difficult to treat. Survival rates for these cancers remain very poor so we urgently need new treatments for patients.

“Boosting the immune system with drugs to treat cancer or even developing a vaccine to prevent cancer are both exciting possibilities, especially if they can be achieved with minimal side effects. We hope that these promising approaches will one day be reproduced in patients.”

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Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Evive Biotech meets primary and secondary endpoints in global Phase III clinical trial for their novel chemotherapy-induced neutropenia treatment | Proteins and Peptides

GSK presents positive clinical data on maternal and older adults RSV candidate vaccines | Vaccines

  • October 22, 2020

GSK presents positive clinical data on maternal and older adults RSV candidate vaccines

  • Phase I/II data presented at ID Week show that the two FDA fast-tracked candidate vaccines trigger robust immune response and are well-tolerated
  • There is currently no vaccine for respiratory syncytial virus (RSV), which causes significant morbidity and mortality in infants and older adults
  • Phase III studies are on track to start in the coming months 

LONDON, UK I October 21, 2020 I GSK today announced that its Respiratory Syncytial Virus (RSV) candidate vaccines for maternal immunisation (GSK3888550A) and older adults (GSK3844766A) were well-tolerated and highly immunogenic in Phase I/II clinical studies. The data were presented virtually at the ID Week Congress.

RSV is a leading cause of respiratory infections such as bronchiolitis (inflammation and congestion of the small airways or bronchioles of the lung) and pneumonia (an inflammatory condition of the lung small air sacs or alveoli) in infants and older adults. It is estimated to cause about 3 million hospitalisations of children under 5 year of age globally[1], and 177,000 hospitalisations of older people in the US alone[2].

Both candidate vaccines contain a recombinant subunit pre-fusion RSV antigen (RSVPreF3) which is believed to trigger the required immune response. The vaccine for older adults also includes GSK’s proprietary AS01 adjuvant system[3] to boost the immune response as this population tends to show weaker immune response to vaccination than younger adults.

The vaccine candidate for older adults was first tested in 48 healthy adults (18-40 years old) and then in 1,005 healthy older adults (60-80 years old) with different dosages of antigen and adjuvant compared with a placebo. The interim data 1-month post-immunisation show that:

  • the candidate vaccine elicited a robust humoral and cellular immunity compared with baseline
  • a close to 10 times increase of protective antibodies (RSVPreF3 IgG and RSV-A neutralising antibodies) was induced in the vaccinated group
  • importantly, the cellular immunity (RSVPreF3-specific CD4+ T-cells) of the vaccinated older adults was boosted to reach similar range to that observed in the younger adults after vaccination with the non-adjuvanted formulation, despite the initial lower baseline level observed in older adults compared with young adults.

The maternal RSV candidate vaccine was tested with 3 different doses compared with placebo in 502 healthy non-pregnant women over monthly visits (Day 8, Day 31 and Day 91 post immunisation). The data show that, compared with baseline:

  • the investigational vaccine was able to rapidly boost the pre-existing immunity at all dose levels, leading to high levels of protective neutralising antibodies
  • at Day 8, a 14-fold increase in RSV-A and RSV-B neutralising antibodies titers was observed.

These two vaccines are part of a tailored, portfolio approach GSK is pursuing with three RSV candidate vaccines – maternal, paediatric and older adults – using different novel technologies aiming to help protect the populations most impacted: infants and older adults. All three candidate vaccines have received FDA fast-track designation.

Emmanuel Hanon, Senior Vice-President and Head of Vaccines R&D, said: “RSV is an infectious disease that can have a very serious impact on families and societies. We are delighted to see these positive results confirming our approach to develop dedicated vaccines building on the strategic use of our platform technologies for the populations most at risk from RSV infections – young infants and older adults. Our portfolio strategy takes into account the unique needs of the immune system of these vulnerable populations and we look forward to progressing these assets to Phase III trials to evaluate their potential efficacy”.

Vaccines for RSV prevention could lead to significant reductions in disease, doctor’s visits, and hospitalisations in infants, toddlers, and older adults, thus having the potential for a significant benefit to individual health in the most vulnerable populations as well as a positive impact on the burden and costs of healthcare systems around the world.

Based on available data and engagement with regulators, Phase III studies for both older adults and maternal RSV candidate vaccines are in preparation and on-track to start in the coming months, while the Phase I/II (in RSV-seronegative infants) and Phase II (in RSV-seropositive infants) studies with the paediatric RSV candidate vaccine are ongoing. Phase I/II safety and immunogenicity data on the paediatric RSV candidate vaccine in RSV-seropositive infants will be presented at European Society for Paediatric Infectious Diseases (ESPID) on 26-29 October 2020.

About GSK’s RSV candidate vaccine for older adults (GSK3844766A)

The Phase I/II study investigates the safety, reactogenicity and immune response of GSK’s RSV candidate vaccine  in older adults aged 60 to 80 (NCT03814590). This candidate vaccine contains GSK’s proprietary AS01 adjuvant, which is also used in GSK’s shingles vaccine. The safety, reactogenicity and immune responses (humoral and cellular-mediated) were first assessed in 48 healthy adults aged 18–40 years who were vaccinated with either 30, 60 or 120 μg dose level of RSVPreF3 non-adjuvanted vaccine or placebo. Following favourable safety outcomes, 1005 adults aged 60–80 years were randomised in a 2-step staggered manner to receive 1 of the 9 RSV vaccine formulations containing either 30, 60 or 120 μg dose level of RSVPreF3, non-adjuvanted or adjuvanted with AS01E or AS01B, or placebo.

Interim data presented at ID Week show that within one-month post-immunisation, the adjuvanted candidate vaccine has been well tolerated with no safety concerns identified. The most frequently reported adverse events were pain at injection site, fatigue and headache.

Moreover, data 1-month post-immunisation show that the candidate vaccine elicited a robust humoral and cellular immunity compared with baseline:

  • High levels of RSVPreF3 IgG antibodies (geometric mean antibody concentrations were 8.4–13.5 for the 18-40 year old vaccinees, and 7.2–12.8 fold-higher in the 60–80-year-old vaccinees) and RSV-A neutralising antibodies (geometric mean antibody titers were 7.5–13.7 in the 18–40 year old vaccinees, and 5.6–9.9 fold-higher in 60–80-year-old vaccinees) were induced in all vaccinated groups.
  • Before vaccination, deficiency of RSVPreF3-specific T-cells (hypothesised to help promote viral clearance) was observed in older adults compared to younger adults. After vaccination, a robust RSVPreF3 CD4+ T-cells response in older adults had been boosted to reach a similar range than the one observed in younger adults, with significantly higher immune response in the groups who received the adjuvanted formulation.

About GSK’s maternal RSV candidate vaccine (GSK3888550A)

The goal of this candidate vaccine is to prevent RSV-associated lower respiratory tract infections in infants during the first months of life by transfer of maternal antibodies – an approach based on GSK’s strong expertise in maternal immunisation acquired through pertussis and flu vaccine programmes. The polyclonal nature of the humoral response boosted by this vaccine could potentially offer broad protection across a large number of RSV strains and addressing the potential issue of virus escape mutation. Maternal immunisation could help to protect infants too young to be immunised from RSV-associated infections in their first months of life – when they are the most vulnerable – without any medical intervention required thanks to the passive transmission of neutralising antibodies from the vaccinated mother to the unborn child in the last weeks of pregnancy.

In this Phase I/II study (NCT03674177), 502 healthy non-pregnant women received 1 dose of either 30, 60 or 120 μg of recombinant protein-based RSVPreF3 or placebo. The safety, reactogenicity and immunogenicity was monitored for 6 months. The data 1-month post-immunisation show that all vaccine dose levels were well-tolerated, with no safety concerns identified: the most frequently reported solicited adverse events were minor and included pain at injection site and headache. 

Moreover, the data show that the candidate vaccine elicited a rapid and persistent immune response in all RSVPreF3 groups. The immune response peaked at Day 8 with a 14-fold increase in neutralising RSV-A and RSV-B titers from baseline. The neutralising titers declined over time but a >6-fold increase was still maintained at Day 91. Anti-RSVPreF3 IgG antibodies were boosted substantially in all groups with geometric mean concentrations of anti-RSVPreF3 IgG antibody (≥ 12-fold at Day 8 and ≥ 6-fold until Day 91 vs baseline). The 60 and 120 μg dose levels of RSVPreF3 were more immunogenic than the 30 μg formulation.

Safety and immunogenicity data from the first time in pregnant women study will be presented in the first half of 2021. The data currently available provide the confidence to advance to late stage clinical work.

About respiratory syncytial virus

Globally, there are an estimated 33 million cases of RSV annually in children less than 5 years of age, with about 3 million hospitalised and approximately 120,000 dying each year from complications associated with the infection. Nearly half of these pediatric hospitalisations and deaths occur in infants less than 6 months of age[4]. According to the Centers for Disease Control and Prevention, virtually all children in the US get an RSV infection by the time they are 2 years old and one to two out of every 100 children younger than 6 months of age with RSV infection may need to be hospitalised[5].

It also represents a significant health threat for older adults, with an estimated 177,000 hospitalisations and 14,000 deaths associated with RSV infections occurring in the US alone[6]. Without robust surveillance systems in several countries, global data on the burden of RSV in older adults is either lacking or likely to underestimate its significance. As global population ages, morbidity and mortality of respiratory infections including RSV to be steadily increasing.

About GSK

GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com.

References

[1] Shi  T. et al, Lancet. 2017;390:946–58

[2] https://www.cdc.gov/features/rsv/index.html

[3] The GSK proprietary AS01 adjuvant system contains QS-21 StimulonTM adjuvant licensed from Agenus Inc. (NASDAQ: AGEN)

[4] Shi  T. et al, Lancet. 2017;390:946–58

[5] CDC – https://www.cdc.gov/rsv/high-risk/infants-young-children.html

[6] CDC – https://www.cdc.gov/features/rsv/

SOURCE: GlaxoSmithKline

GSK sees 'robust immune response' from RSV vaccine hopefuls

GSK sees ‘robust immune response’ from RSV vaccine hopefuls

  • October 21, 2020

Cold viruses often don’t get much of a look when it comes to R&D; they are annoyances, but ones that usually make us feel miserable for a few days then clear up.

But some cold viruses can hit vulnerable people much harder, leading to pneumonia and hospitalizations. These are colds caused by the respiratory syncytial virus (RSV), which, in the elderly and in children under 5, can cause serious complications and sometimes can prove fatal.

In younger children, it can cause bronchiolitis (inflammation and congestion of the small airways or bronchioles of the lung) and pneumonia in both infants and the elderly, and it’s thought to cause about 3 million hospitalizations of children under 5 globally, with around 177,000 hospitalizations of older people in the U.S.

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There have been a number of Big Pharma attempts at a vaccine, but the road has been fraught with setbacks and flops. There is a monthly preventive shot from Swedish Orphan Biovitrum’s Synagis used against RSV in high-risk infants, but a fully protective vaccine remains elusive.

RELATED: Novavax plummets after another phase 3 RSV study miss, this time in infants

GlaxoSmithKline took a step closer to finding that vaccination, announcing data from several candidates at IDWeek 2020 from several midstage trials, as it now plots a late-stage make-or-break series of tests.

The RSV candidate vaccines were for two distinct groups: one for maternal immunization (GSK3888550A) and one for older adults (GSK3844766A). Top-line, GSK says both “were well-tolerated and highly immunogenic in phase 1/2 clinical studies.”

The former was tested with three different doses compared with placebo in 502 healthy non-pregnant women over monthly visits and showed the vaccine was able to “rapidly boost the preexisting immunity at all dose levels, leading to high levels of protective neutralising antibodies.”

And, just over a week after the shot, GSK said it saw a 14-fold increase in RSV-A and RSV-B neutralizing antibody titers. The idea is for the vaccine, which uses the Big Pharma’s AS01 adjuvant system, to give pregnant women the ability to confer immunity to their unborn children.

This has not been proven in this latest study, but GSK said it will be presenting data from pregnant women in the first half of next year to see whether its theory is borne out.

The latter candidate, in older adults, was first tested in 48 healthy adults (18-40 years old) and then in 1,005 healthy older adults (60-80 years old) with different dosages of antigen and adjuvant compared with a placebo.

The interim data, out one month after the shot, showed a “robust humoral and cellular immunity compared with baseline” and “a close to 10 times increase of protective antibodies” in the vaccinated group.

A phase 3 program for both patient populations is expected to begin in the “coming months.” Several other early-to-midstage trials are also ongoing in younger children either with exposure to RSV or without, with data for RSV-seropositive infants to be published at the European Society for Paediatric Infectious Diseases next week.

All three candidate vaccines have been given an FDA fast-track label.

“RSV is an infectious disease that can have a very serious impact on families and societies,” said Emmanuel Hanon, GSK senior vice president and head of vaccines R&D. “We are delighted to see these positive results confirming our approach to develop dedicated vaccines building on the strategic use of our platform technologies for the populations most at risk from RSV infections: young infants and older adults.

“Our portfolio strategy takes into account the unique needs of the immune system of these vulnerable populations and we look forward to progressing these assets to Phase III trials to evaluate their potential efficacy.”

GSK is in a race with Johnson & Johnson and Moderna, which are also hard at work on vaccinations for COVID-19, for an RSV shot.

All eyes on a hurdle race for a SARS-CoV-2 vaccine

All eyes on a hurdle race for a SARS-CoV-2 vaccine

  • October 19, 2020

The catastrophic global health and socioeconomic impact of COVID-19, together with the absence of any clearly effective preventive or therapeutic remedies, has created a massive unmet medical need. Rapid responses by governments, academia and industry have already resulted in the production of more than 180 vaccine candidates1, 42 of which are being tested in humans at the time of writing. The considerable design flexibility of newer types of vaccine technology gave these candidates a head start in the race. Some of the candidates, which are based on nucleic acids (such as messenger RNA), entered human trials2 as early as March. In this issue, Mulligan et al.3 and Sahin et al.4 report clinical-trial results for a COVID-19 vaccine called BNT162b1, which contains mRNA that encodes part of a protein found on the surface of the SARS-CoV-2 coronavirus. This vaccine, made by Pfizer and BioNTech, was tested in adults in a combined phase I and phase II clinical trial.

The primary goal of phase I/II vaccine clinical trials is to evaluate short-term safety, check dosage and assess aspects of the body’s reaction to the vaccine — effects known as reactogenicity. Reactogenicity could include localized pain, redness or swelling at the site of vaccine injection, as well as systemic symptoms elsewhere in the body, such as fever, muscle pain and headache. Some reactogenicity might be expected as a normal sign that the immune system is generating a response to the vaccine, and so early-phase safety evaluation focuses particularly on more-serious effects.

The secondary goal of these early-stage clinical trials is to assess immunogenicity — the ability of a vaccine to stimulate a detectable immune response to the vaccine target (Fig. 1). This typically involves assessing components of what is known as the adaptive branch of the immune system. The features of interest are vaccine-specific antibody responses and immune cells called CD4 (or helper) T cells and CD8 (cytotoxic) T cells. These T cells can directly target cells infected with the virus, or collaborate with antibody-producing B cells. The best vaccines elicit long-lasting responses that produce ‘neutralizing’ antibodies, which act to hinder or prevent an infectious agent from causing illness5. Once phase I and II trials have been completed, a phase III study can be conducted to determine whether the vaccine affects how susceptible people are to a disease.

Figure 1

Figure 1 | Assessing a vaccine that targets the SARS-CoV-2 coronavirus. Mulligan et al.3 and Sahin et al.4 report vaccine clinical-trial results for a combined phase I and phase II study. a, The vaccine contains messenger RNA in a lipid nanoparticle that is taken up by human cells. The mRNA encodes a region of the coronavirus spike protein termed the receptor-binding domain (RBD). b, After vaccination, the authors monitored the trial participants’ responses. One type of response assessed was ‘reactogenicity’ — signs of the body’s reaction to vaccination, such as local swelling at the injection site or systemic effects elsewhere in the body, for example, headache or fever. Another type of response assessed, called immunogenicity, relates to signs of an immune-system defence against the vaccine target, as indicated by the presence of RBD-specific antibodies, and RBD-specific T cells that produce the signalling molecule interferon-γ. The reactogenicity and immunogenicity results were acceptable for this early-stage clinical-trial work.

Mulligan, Sahin and their respective colleagues provide the first insights into the reactogenicity and immunogenicity of BNT162b1. This vaccine consists of an injected mRNA that encodes part of the ‘spike’ protein of SARS-CoV-2 — a region of the protein known as the receptor-binding domain (RBD), which enables the virus to engage with and infect human cells. Antibodies that bind to the RBD provide a way of interfering with a key starting point in the SARS-CoV-2 cycle of infection, and so attack this viral Achilles heel. Accordingly, the RBD and the spike protein are the targets of most of the vaccine candidates.

Mulligan and colleagues gave the vaccine at one of 3 doses (10, 30 and 100 micrograms) to 36 healthy adults (age range 18–55 years), with 9 other participants receiving a placebo treatment. Sahin and colleagues’ trial did not have a placebo control group, and enrolled 60 participants who received the vaccine at one of 5 doses (1, 10, 30, 50 and 60 µg). The participants in both trials in all but the highest dosage groups (100 and 60 µg, respectively) received 2 vaccinations at 3-week intervals, in what is known as a prime–boost regimen. This approach can determine whether the addition of a second ‘booster’ vaccination enables a strong immune response to develop. More than 80% of the study participants were white, and around 2% were Black.

Although no serious adverse events were reported, notable reactions at the injection site or elsewhere in the body were frequent. For example, of the participants in the medium-dose (30 µg) group of both studies, 96% reported pain at the injection site and 92% reported headaches. Moreover, the prevalence of these reactions was dose dependent, and increased after the booster immunization, so a second injection was not given to the highest-dose groups. In addition, lymphocytes — white blood cells of the immune system (which include T cells and B cells) — were reduced in number in most vaccinated individuals, but returned to normal 6–8 days after vaccination.

Vaccine-induced anti-RBD antibody levels were quantified at multiple time points. However, the latest time point assessed was at only two (Mulligan et al.) or three (Sahin et al.) weeks after the booster injection. All vaccinees developed low-level anti-RBD antibody responses after the first vaccination. As expected, the antibody levels depended on the vaccine dose, and they increased 10–15-fold after the booster. By three weeks after the booster, the antibody levels dropped. Antibody-mediated SARS-CoV-2 neutralization, as assessed by in vitro experiments, followed a similar pattern, and it also declined three weeks after the booster. This result stresses the importance of long-term follow-up to understand the durability of vaccine-induced immune responses. A decline in the response is expected over time, and such a follow-up is needed to determine the rapidity of this decline.

With the exception of the group who received the lowest vaccine dose, levels of neutralizing-antibodies against SARS-CoV-2 compared favourably with those in blood samples taken from people who had recovered from COVID-19 — commonly referred to as COVID-19 convalescent serum or plasma. Crucially, the magnitude and dynamics of the elicited antibody response indicate that a booster dose is essential for this vaccine.

Sahin and colleagues measured the responses of CD4 and CD8 T cells before the first vaccination and one week after the booster. Although most vaccinees showed convincing responses, the strength of the T-cell responses, as measured by the production of immune-system signalling molecules called cytokines, varied between participants, and there was no clear dose dependency in the responses.

In terms of what we have learnt from the results of these phase I/II clinical trials, the reactogenicity and early safety profile seem acceptable. However, it should be remembered that, as the authors acknowledge, this was a small group of individuals, and it was missing people from key age profiles and at-risk groups. The average age of the participants in the two trials was 35 and 37, respectively.

In another study6, Pfizer and BioNTech reported a clinical trial that compared BNT162b1 with a different version of the vaccine, termed BNT162b2, that uses mRNA encoding the full-length spike protein. Among older adults, aged between 65 and 85, those vaccinated with BNT162b2 showed less systemic reactogenicity than did people vaccinated with BNT162b1. BNT162b2 was therefore selected to go forward to an ongoing phase II/III large-scale clinical trial6.

So what do the data tell us about whether the vaccine generates immunity to COVID-19, and about the correlates of immune protection — the quality and quantity of vaccine-induced antibody and T-cell responses elicited? The results are encouraging but inconclusive. The presence of neutralizing antibodies is correlated with protection from SARS-CoV-2 infection in monkeys79, and there are anecdotal reports for humans that are consistent with this10. However, a definitive interpretation of such data is complicated by the lack of standardized tests for assessing T-cell and neutralizing-antibody responses. Approaches to tackle this shortcoming are already being developed, for example by the SARS-CoV-2 Neutralization Assay Concordance Survey (go.nature.com/3iqh0jp), and the results should help to provide a way of comparing different vaccine candidates.

Taken together, the early clinical data for the Pfizer/BioNTech vaccine candidate hold promise, but many questions remain for this and other mRNA vaccines that target SARS-CoV-2. For example, what is the optimal dose, and what would be the best timing for a booster vaccination? How long does the vaccine-induced immune response last? Is the vaccine safe and effective in people with underlying health conditions, or those of minority-racial and -ethnic backgrounds, who are disproportionately affected by COVID-19? Whether the vaccine is safe in children should also be tested. In addition, there are logistical hurdles to consider when distributing and administering a vaccine that requires transport and storage at −80 °C. Above all, it needs to be established that the vaccine-elicited immune response prevents infection and disease.

Data to come from the ongoing large-scale phase II/III clinical trial — revealing efficacy and longer-term safety profiles — will be crucial for answering some of the remaining questions. This is especially important for pioneering RNA-based vaccines, such as BNT162b1 and BNT162b2, that lack the extensive safety record of vaccine candidates developed using a conventional approach.

The good news is that the final hurdle on the way to the finishing line — the completion of a properly controlled phase III clinical trial — is in sight. Ideally, this process will not be jeopardized by a premature rush, through an Emergency Use Authorization by the US Food and Drug Administration or other international regulators, to get a vaccine into use in the clinic before the trial has generated sufficient safety and efficacy information. As in any hurdle race, skill, speed and judgement are all needed to successfully and safely cross the finishing line.

Increased Humoral Immune Response Against C. Diff Toxins Linked to Mild Disease

Increased Humoral Immune Response Against C. Diff Toxins Linked to Mild Disease

  • October 19, 2020

Findings from a new study showed an association between high serum immunoglobulin G (IgG) and immunoglobulin A (IgA) levels and milder cases of Clostridium difficile (C. difficile).

Specifically, this association was modulated by the two serum antibodies targeting of both toxins A (TcdA) and B (TcdB), which play an essential role in the pathogenesis of the disease.

Investigators from Tel Aviv University and Tel Aviv Sourasky Medican Center conducted a case-control study to determine the risk factors of C. difficile infection (CDI) and evaluate the link between humoral immune response and CDI severity.

Thus, their analysis consisted of a total of 50 patients with CDI, 62% of whom were female. This represented a subset of 140 total CDI patients who were enrolled in their study.

They categorized CDI patients according to severity—severe disease was defined as leukocytosis with a white blood cell count of ≥15,000 cells/μL, decreased blood albumin (<30 g/L) or a rise in serum creatinine level ≥1.5 times the premorbid level. Any patient who did not fulfill any of these requirements were considered to have a mild case.

Additionally, they analyzed 52 patient controls who were not suffering from diarrhea, where 56% were female. In total, they had enrolled 140 controls.

Both CDI patients and controls were matched by age, sex, hospitalization ward (medical or surgical), and number of hospitalization stays. 

The mean age between the CDI and control groups were 79.2% years and 82.7%, respectively.

The investigators collected stool specimens from the both groups to test for C. difficile. Blood samples were also collected, and the levels of serum IgG and IgA antibodies against TcdA and TcDB were measured.

Overall, they found that patients with CDI presented with higher geometric mean titers (GMT) values of serum IgG antibody against TcdA when compared with the control group (20.1 EU vs 11.6 EU, respectively; P = .0001).

The GMT values of serum IgG against TcdB were also higher for the CDI group than for the control (18.0 EU vs 12.0 EU, respectively; P = .04).

They also noted that similar trends were observed for IgA antibodies, but the differences were not statistically significant.

In terms of associations for C. diff severity, they found that GMT values of serum IgA against TcdB was significantly higher among CDI patients with mild disease as compared with patients with severe disease (9.2 EU vs 4.9 EU, respectively; P = .023).

Similar but non-statistically significant trends were noted found for IgA and IgG levels against TcdA, as well as for IgG against TcdB.

“Limiting the analysis to sera that were collected at days 7–14 following the diagnosis of C. difficile showed significantly higher IgG levels against TcdA and TcdB in patients with mild CDI compared to patients with severe CDI,” they wrote.

Furthermore, they found significant correlations between serum IgG levels and TcdA and TcdB (Spearman’s r = 0.31). Other strong correlations included IgA levels against TcdA and TcDB (r = 0.53) and IgG and IgA levels against TcdB (r = 0.43).

Although there remains great uncertainty behind the mechanism that can explain the protective effect of serum IgA and IgG antibodies against C. diff toxins, the investigators nonetheless suggested implications for the findings.

“Based on the current evidence from observational studies and our new findings, the concept of presenting antigens that can prime or boost the immune system towards the production of antitoxin circulating antibodies seems a sensible approach for developing preventive and therapeutic vaccines and technologies for CDI,” the team wrote.

The study, “Enhanced Humoral Immune Responses against Toxin A and B of Clostridium difficile is Associated with a Milder Disease Manifestation,” was publshed online in Journal of Clinical Medicine.

SARS-CoV-2 vaccine safely induces an immune response

SARS-CoV-2 vaccine safely induces an immune response

  • October 16, 2020

The Chinese COVID-19 vaccine candidate BBIBP-CorV elicited an antibody response in all recipients, according to preliminary Phase I/II trial data.

vial labelled 'COVID-19 Vaccine'

Preliminary data from the Phase I/II trial testing the safety of the BBIBP-CorV vaccine, based on an inactivated whole SARS-CoV-2 virus, suggested the vaccine candidate is safe and can elicit an antibody response.

The study included participants aged 18 to 80 years old, all of which had antibody responses. Participants aged 60 plus were slower to respond, taking 42 days before antibodies were detected in all recipients, compared with 28 days for participants aged 18-59. Antibody levels were also lower in those aged 60-80 years compared to the younger participants (Mean neutralising antibody titre 42 days after receiving a 8μg vaccine dose was 228.7 for people aged 18-59 and 170.9 for those aged 60-80).

The trial was not designed to assess vaccine efficacy, so the investigators cannot comment on whether the antibody responses induced by BBIBP-CorV are sufficient to protect from SARS-CoV-2 infection.

Professor Xiaoming Yang, one of the authors of the study, from the Beijing Institute of Biological Products Company Limited, China, said: “Protecting older people is a key aim of a successful COVID-19 vaccine as this age group is at greater risk of severe illness from the disease. However, vaccines are sometimes less effective in this group because the immune system weakens with age. It is therefore encouraging to see that BBIBP-CorV induces antibody responses in people aged 60 and older, and we believe this justifies further investigation.”

Currently, 42 potential COVID-19 vaccines are undergoing clinical trials. There is a huge variety in type, ranging from DNA plasmid vaccines to inactivated virus vaccines, adenovirus-vectored vaccines to RNA vaccines, protein subunit vaccines and virus-like particle vaccines. Some of these have already been shown to be safe and to elicit immune responses in early clinical trials.

The BBIBP-CorV vaccine includes an inactivated SARS-CoV-2 virus that was isolated from a patient in China and grown in the lab using cell lines. The virus is inactivated using a chemical called beta-proprionolactone for inclusion in the vaccine. BBIBP-CorV also includes an aluminium hydroxide adjuvant, which boosts immune responses.

The first phase of the study was designed to find the optimal safe dose for BBIBP-CorV. It involved 96 healthy volunteers aged between 18 and 59 years and a second group of 96 participants aged between 60 years and 80 years. Within each group, the vaccine was tested at three different dose levels (2μg, 4μg and 8μg, 24 participants per group), with two vaccinations administered on day zero and day 28. A fourth group within each age range (24 participants in each age group) were given two doses of a placebo vaccine. A total of 144 participants received the vaccine and 48 received the placebo in Phase I of the study.

The second phase of the study was designed to identify the optimal timing schedule for vaccination. A total of 448 participants aged between 18 and 59 years were randomly assigned to receive either one 8μg shot of vaccine or placebo; or two shots of 4μg vaccine or placebo at zero and 14 days, zero and 21 days or zero and 28 days. In this second phase, there were 112 participants per group, with 336 receiving the vaccine and 112 receiving the placebo.

…the investigators cannot comment on whether the antibody responses induced by BBIBP-CorV are sufficient to protect from SARS-CoV-2 infection”

Participants were asked to report any adverse events for the first seven days after each vaccination and these were verified by the research team. Thereafter, participants recorded any adverse events using paper cards for the following four weeks. During Phase I, laboratory tests were carried out after the vaccinations to assess kidney, liver and other organ functions. Blood samples were taken to test antibody levels for SARS-CoV-2 before and after vaccination.

No serious adverse events were reported within 28 days of the final vaccination. The most common side effect was pain at the injection site of vaccine recipients. A small number of participants reported experiencing a fever. There were no instances of clinically significant changes in organ functions detected in laboratory tests in any of the groups.

The greatest antibody responses were elicited by two 4μg doses of the vaccine at either zero and 21 days or zero and 28 days (mean neutralising antibody titres 28 days after second vaccination were 282.7 for two 4μg injections at day zero and 21; and 218.0 for two 4μg injections at day zero and 28).

Professor Xiaoming Yang said: “Our findings indicate that a booster shot is necessary to achieve the greatest antibody responses against SARS-CoV-2 and could be important for protection. This provides useful information for a Phase III trial.”

The authors noted some limitations with the study, including the short duration of follow up at just 42 days. They also highlighted that the study did not include children and adolescents aged under 18. Trials with these groups will be carried out when the full analysis of data from adult groups is completed, the researchers say.

The findings were published in The Lancet Infectious Diseases.

Bonn Group launches ''immunity-boosting'' herb and seeds bread

Chinese COVID-19 vaccine candidate shows promise in human trial: Study

  • October 16, 2020
Beijing, Oct 16 (PTI) One of China”s leading COVID-19 vaccine candidates, called BBIBP-CorV, was shown to be safe and elicited immune response in a small early-phase human trial, researchers said on Friday.

A previous clinical trial reported similar results for a different vaccine that is also based on inactivated whole SARS-CoV-2 virus, but in that study the vaccine was only tested in people aged under 60 years.

The latest study, published in The Lancet Infectious Diseases journal, included participants aged between 18 and 80 years, and found that antibody responses were induced in all recipients.

Participants aged 60 and over were slower to respond, taking 42 days before antibodies were detected in all recipients compared with 28 days for participants aged 18-59, the researchers said.

Antibody levels were also lower in those aged 60-80 years compared with those aged 18-59, they said.

The BBIBP-CorV vaccine used in the study is based on a sample of the virus that was isolated from a patient in China.

Stocks of the virus were grown in the lab using cell lines and then inactivated using a chemical called beta-proprionolactone.

BBIBP-CorV includes the killed virus mixed with another component, aluminium hydroxide, which is called an adjuvant because it is known to boost immune responses.

The trial was not designed to assess efficacy of the vaccine, so it is not possible to say whether the antibody responses induced by the vaccine, called BBIBP-CorV, are sufficient to protect from SARS-CoV-2 infection, according to the researchers.

“Protecting older people is a key aim of a successful COVID-19 vaccine as this age group is at greater risk of severe illness from the disease,” said Professor Xiaoming Yang, one of the authors of the study, from the Beijing Institute of Biological Products Company Limited.

“However, vaccines are sometimes less effective in this group because the immune system weakens with age. It is therefore encouraging to see that BBIBP-CorV induces antibody responses in people aged 60 and older, and we believe this justifies further investigation,” said Yang.

There are currently 42 vaccines for COVID-19 in clinical trials, the researchers noted.

These vary in type and include DNA plasmid vaccines, inactivated virus vaccines, adenovirus-vectored vaccines, RNA vaccines, protein subunit vaccines and virus-like particle vaccines, they said.

Some of these have already been shown to be safe and to elicit immune responses in early phase clinical trials.

The first phase of the study involved 96 healthy volunteers aged between 18 and 59 years and a second group of 96 participants aged between 60 years and 80 years.

Within each group, the vaccine was tested at three different dose levels, with two vaccinations administered on day 0 and 28.

A fourth group within each age group were given two doses of a placebo vaccine.

In the second phase of the study, 448 participants aged between 18 and 59 years were randomly assigned to receive either one 8 microgramme shot of vaccine or placebo, or two shots of 4 microgramme vaccine or placebo.

No serious adverse events were reported within 28 days of the final vaccination, and the most common side effect was pain at the injection site, the researchers said.

There were no instances of clinically significant changes in organ functions detected in laboratory tests in any of the groups, they said.

The greatest antibody responses were elicited by two 4 microgramme doses of the vaccine at either days 0 and 21 or 0 and 28, according to the resaerchers.

“Our findings indicate that a booster shot is necessary to achieve the greatest antibody responses against SARS-CoV-2 and could be important for protection. This provides useful information for a phase 3 trial,” Yang said.

The researchers noted some limitations with the study, including the short duration of follow up at just 42 days.

They also highlighted that the study did not include children and adolescents aged under 18.

” More studies are needed to establish whether the inactivated SARS-CoV-2 vaccines are capable of inducing and maintaining virus-specific T-cell responses,” said Professor Larisa Rudenko from the Institute of Experimental Medicine, Russia, who was not involved in the study.

This is because CD4-positive T-cell help is important for optimal antibody responses, as well as for cytotoxic CD8-positive T-cell activation, which, in turn, are crucial for viral clearance if neutralising antibody-mediated protection is incomplete, Rudenko said. PTI SAR
SAR



Disclaimer :- This story has not been edited by Outlook staff and is auto-generated from news agency feeds. Source: PTI


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OPINION: The flu vaccine is a necessity, this year more than ever

OPINION: The flu vaccine is a necessity, this year more than ever

  • October 15, 2020


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Flu season is often characterized as a time where people are bound to get sick, and, for the most part, people view the flu as an unfortunate inconvenience that has them bedridden for a few days at most. Because of the unusual circumstances surrounding the COVID-19 pandemic, common illnesses such as the flu can cause an array of problems for people who are infected, this year in particular.

In light of the pandemic, IU is now requiring its students and employees who are regularly on campus to get a flu vaccine before Dec. 1. They are also offering the vaccines at no cost to its students this semester, which is an amazing initiative that can ultimately save lives on campus.

It’s great IU is providing and even requiring flu vaccinations for its students this year, and it’s essential students take initiative and get a flu vaccine as early as possible.

Getting your flu shot early is the best way to go about getting your vaccination. It takes about two weeks for the antibodies needed to fight the flu to develop in your immune system. If you haven’t scheduled your shot yet, it’s something you should consider looking into as soon as you can.

People can be indifferent when it comes to a flu vaccine. It’s a seasonal vaccine, meaning it is only effective on a year-to-year basis. Some people go out of their way to ensure they are vaccinated every year, while others only get it if it’s convenient to do so, such as at a doctor’s appointment or at their place of employment.

Others don’t get the flu vaccine, even when it is convenient to do so. Flu vaccine coverage for adults in the U.S. was 45.3% during the 2018-19 season. Yearly coverage is an important factor in determining the severity of a particular flu season because it indicates how many people already have an immune boost that helps them fight off the disease.

Because of the COVID-19 pandemic, these common and usually minor diseases like the flu can cause a multitude of issues, primarily the complications that can occur if someone is infected with both the flu and COVID-19 at the same time.

If this were to happen, the diseases together can cause respiratory issues and progress to pneumonia, or even respiratory failure. They can have long-term effects on the respiratory system and can inhibit the lung’s ability to absorb oxygen, which affects all the other major organ systems in the body.

A flu shot is an easy and effective way to reduce the chances of becoming seriously ill from these diseases, no matter how old you are. Even if you don’t think you are at risk, this is something that can happen to anyone of any health background.

The flu vaccine protects not only yourself, but also those around you who may not be able to get a vaccination due to other underlying conditions. It boosts your own immune system, and it plays an essential role in herd immunity.

In addition to this, having a large percentage of people getting a flu shot will play a major role in keeping hospitalizations down, and prevent an overwhelmed health care system. This way, people who truly need help get the attention they need, and unnecessary deaths can easily be avoided.

It’s important to stay vigilant during these uncertain times, even though it can be difficult. It may seem like a hassle now to schedule a flu shot, but the preventative actions we take today can save lives tomorrow.

Aidan Kramer (she/her) is a freshman studying microbiology and environmental science. After graduating, she plans to attend medical school and pursue a career in pathology.

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Bioengineering technique that boosts protein production could lead to effective COVID-19 vaccine

Researchers create multi-functional nano-vaccine to prevent toxoplasmosis

  • October 14, 2020

Fighting clever parasites requires smart vaccines that can trigger critical immune responses. A University of Chicago-based research team has found a novel way to do that.

These experts, specialists in toxoplasmosis and leaders in vaccine design, have focused on one of the most frequent parasitic infections of humans.

The parasite, Toxoplasma gondii, can cause lifelong infection. It lives in the brain (and sometimes the eyes) of about 30 percent of all humans. When someone drinks contaminated water, eats infected undercooked meat or is exposed to these parasites in soil, it can result in lasting damage.

Infection from unrecognized exposure to this microscopic parasite can harm the eyes, damage the brain and, in some cases, lead to death. Toxoplasmosis, according to the CDC, is the second most frequent cause of foodborne-associated death in the United States.

These parasites tend to attack unborn babies, newborns, children and adults. While most healthy adults who are exposed to the parasite never experience any serious symptoms, dormant, unrecognized, smoldering infections can emerge years later in immune-compromised patients. There is currently no vaccine to protect people from this infection.

“We urgently need a vaccine, as well as new and better medicines, to prevent and treat this infection,” said the study’s senior author, Rima McLeod, MD, Professor of Ophthalmology and Visual Science and Pediatrics at University of Chicago and a leading authority on toxoplasmosis.

“Millions of people suffer from these infections,” McLeod said. These neglected infections are often detected too late to prevent irreversible damage, and some patients die if the infection is untreated. Until now, no vaccine has been available for humans and no known medicine in clinical use has been able to eliminate the chronic, encysted form of Toxoplasma.

In an article published in the journal Scientific Reports (Nature), the research team unveiled a clever “immunosense” approach – the use of Self-Assembling Protein Nanoparticles (SAPNs). These have been engineered to boost each component of the immune system.

The goal is to protect humans from this common, harmful and sometimes lethal parasite.”Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A*11:01, HLA-A*02:01 and HLA-B*07:02 transgenic mice” was published online on October 12, 2020.

The team used cell-based and murine models. These mouse models have human immune-response genes to mimic how people can fight the infection. The SAPN scaffold serves as a stimulus, boosting the innate immune response and delivering components of the vaccine to relevant target cells.

“Especially important,” McLeod said, “these novel SAPNs have been engineered to have the size, shape and ability to produce immune responses against Toxoplasma gondii. This triggers a protective effect.”

The team’s approach has been quickly adopted by other investigators. There is ongoing work to immunize against herpetic eye disease, SARS-CoV-2 (COVID19), HIV, malaria and influenza viruses.

The researchers found that their SAPN scaffold can fold reliably into a stable shape. As the immune system perceives it as a foreign invader stimulating a protective immune response, the scaffold can incorporate components that stimulate an immune response against the genetic variants of the parasite.

This can be tailored for people of differing genetic backgrounds. The vaccine becomes a multisystem targeting weapon. The researchers named their new weapon “ToxAll.” They describe it as a “multi-epitope, multi-functional, toxoplasmosis nano-vaccine.”

It contains crucial immunity-stimulating components, mixed with an adjuvant, known as GLA-SE, that appears to be powerful and safe in humans. This type of vaccine, with components from plasmodia, has already been tested in primates for malaria, and is moving into the clinic.

Prior infections with T.gondii before pregnancy can protect a pregnant woman from passing the infection to her unborn child. But when a mother first acquires the infection during pregnancy – before her body can mount an immune response – the parasite can cause significant harm to the unborn child.

The investigators first created a live, attenuated vaccine that can protect mice against toxoplasmosis. Prior natural infection of humans can confer protection, and live vaccines could protect mice. These live vaccines, however, can have safety concerns.

ToxAll was created as a synthetic vaccine that could stimulate danger signals, alerting the immune system to focus on foreign invaders. A crucial part of the process is to create a design with the right properties, assembling particles into predictable shapes that resemble viruses, then enabling the fragments of components of the parasite to educate the “adaptive memory” of the immune system. This creates a long-lasting immune response, including antibodies and protective T lymphocytes.

Protection with the full SAPN, at this point, is not yet available, “but is under development with promising results,” McLeod said. The team is working to expand the use of additional fragments of the parasite. They hope to create a next generation vaccine that could provide lasting immunity against toxoplasmosis – one that could offer a novel, safe, synthetic vaccine to prevent this disease.

The next step is to develop vaccines as part of a “toolbox” that also includes new medicines and novel use of older medicines for prevention and treatment of toxoplasmosis. The team has applied their clinical and laboratory experiences to understand the infection and devise ways to prevent it, using immunology, genetics, bioinformatics and systems biology to develop and enhance the vaccine and make certain it can help humans worldwide.

We now think we are reaching the next stage. Our toolbox could be developed to prevent and treat human T. gondii and P. falciparum infections. This approach for vaccines can generate innate immunity, cell-mediated adaptive immunity, and host-neutralizing antibodies that are critical to protect against different pathogens.”


Rima McLeod, MD, Study Senior Author and Professor, Department of Ophthalmology and Visual Science and Pediatrics, Leading Authority on Toxoplasmosis, University of Chicago

Source:

Journal reference:

Bissati, K. E., et al. (2020) Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A*11:01, HLA-A*02:01 and HLA-B*07:02 transgenic mice. Scientific Reports. doi.org/10.1038/s41598-020-73210-0.

Coronavirus Vaccine Makers Are Not Mass-Slaughtering Sharks

Coronavirus Vaccine Makers Are Not Mass-Slaughtering Sharks

  • October 13, 2020

Several companies in the race for a coronavirus vaccine have stumbled upon a new and unexpected hurdle: activists protesting the use of a substance that comes from sharks in their products.

The oily compound, called squalene, is churned out by shark livers and has immunity-boosting powers, which has led several companies to use it as an ingredient in vaccines. A group called Shark Allies has mounted a campaign calling on the Food and Drug Administration and other regulatory bodies to halt the sourcing of the compound from sharks, warning that mass distribution of a coronavirus vaccine could require harvesting tissue from more than 500,000 sharks.

The call to action made headlines around the globe. But the story on shark squalene isn’t as clear-cut as it might at first seem.

Companies commonly use squalene as a moisturizing additive in cosmetics and sunscreens. But the substance has also been occasionally used in vaccines as an adjuvant — a chemical that kick-starts the immune system into action, driving stronger, longer-lasting protection against disease.

Although adjuvants aren’t necessary for all vaccines, they can make or break certain recipes. By boosting products’ immunity-priming powers, they can also increase the immunization’s efficiency, giving the vaccine’s ingredients more bang for their buck and freeing up supplies for more doses.

Shark livers are considered among the best sources of the compound. Between 63 million and 273 million sharks die at the hands of humans each year, and liver oil is harvested from at least a couple million of them, according to Catherine Macdonald, a shark biologist in Florida.

Two of the companies under the scrutiny of Shark Allies are GlaxoSmithKline and Seqirus, which each manufacture adjuvants that contain about 10 milligrams of squalene per dose. Those ingredients are found in a number of coronavirus vaccines currently being tested in humans, including products from Sanofi, Medicago and Clover Biopharmaceuticals, which have all partnered with GSK.

According to one estimate, between 2,500 and 3,000 sharks are needed per metric ton of squalene. Shark Allies extrapolated from these statistics to arrive at their widely quoted numbers tabulating the potential ecological toll on sharks.

Such estimates are difficult to make.

Dr. Macdonald pointed out that sharks — of which there are more than 500 species worldwide — vary in size, weight and liver squalene content. The number of sharks required to yield enough squalene-adjuvanted vaccine doses to treat everyone on Earth is thus likely to be a “huge range,” she said. Her own calculations for this statistic stretch between tens of thousands and more than a million, depending on how many doses are needed per person.

It’s also the case that of the dozens of vaccine candidates in clinical trials in people, most don’t include squalene. To only rely on vaccines that use shark-based squalene, “a ton of other promising candidates would have to fail — they would have to be the last vaccines standing,” said Saad Omer, a vaccine expert at Yale University. A more plausible scenario would probably involve the distribution of several products made by multiple companies.

Squalene has plenty of plant and animal sources (including humans, who produce it to lubricate and protect their skin).

But squeezing squalene out of plants is a pain, while “shark oil is cheap and easy to come by,” said Stefanie Brendl, the executive director of Shark Allies.

“We feel that’s not an excuse,” she said.

She pointed to Amyris, a California-based company, which has been pursuing a synthetic alternative.

Evan Berland, director of U.S. corporate communications for GSK, said the company “is committed to environmental stewardship and is actively exploring the potential for alternative sources of its raw materials when possible.”

No squalene alternatives, however, would be available “within the time frame of the Covid-19 pandemic,” he said.

Joanne Cleary, a Seqirus spokeswoman, said her company was in a similar situation. “More will need to be done to research plant-based or synthetic alternatives before they can be used in vaccines,” she said.

Swapping adjuvants, or even adjuvant sources, isn’t trivial, Dr. Omer said. Each product has to be refined and tested to ensure it’s safe and effective, and work its way — often ploddingly — through the necessary regulatory steps.

Neither GSK nor Seqirus named their suppliers. But GSK said the sharks their squalene came from were “typically caught for other purposes.”

Dr. Macdonald said it’s impossible to answer questions about the exact number of sharks that would be killed explicitly for their squalene. Fishers capture sharks for their meat or fins, or simply as bycatch; in many cases, the oil pulled from their bodies might otherwise have been discarded.

No.

Even the Shark Allies team does not think the vaccine industry is “going out and hunting down sharks — we are not saying that at all,” Ms. Brendl said. Nor do they wish for companies to terminate or delay coronavirus vaccine production.

“But there are alternatives to shark adjuvants,” she said. “Start testing them.”

Dr. Macdonald and others noted that vaccine manufacturers by no means bear the brunt of the responsibility for hoarding shark liver oil. Most fish-sourced squalene is still routed to cosmetics — “much less important things” than vaccines, said Jasmin Graham, a shark biologist at Mote Marine Laboratory in Florida.

Crafting more sustainable fishing practices, she said, could help tackle multiple issues at once.

“I don’t think we should demonize the people trying to save our lives,” Ms. Graham said. “There are much larger, more important hills to die on.”

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