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.

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.

MAPI Broiler-at-pan.jpg

Boosting chickens own immune response could curb disease

  • October 8, 2020

Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks.

According to the University of Illinois, various approaches — developed over decades — have been used to control coccidiosis, but the disease remains widespread. Now, recent research from the University of Illinois supports the use of immunomodulatory and antioxidant feed additives to reduce the effects of coccidiosis.

“In the last two decades, partially to get around the parasite’s resistance to pharmaceuticals, vaccination has become more prevalent. That’s when I got interested, because nutrition is a key element in the effectiveness of vaccines. Diet and health go together in that way,” said Ryan Dilger, associate professor in the department of animal sciences at the University of Illinois and principal investigator on the research. “So, what we’re talking about here is not a vaccine. Instead, we used nutritional technologies to disrupt the normal reproductive cycle of the parasite.”

When a chicken picks up the parasite, of which there are seven major Eimeria species affecting broilers, its body mounts an immune response, starting with a cascade of inflammatory proteins known as cytokines. These cause the bird to stop eating and rest, so the immune system can do its work. In normal disease progression, an anti-inflammatory mediator known as interleukin-10 (IL-10) is eventually produced to keep the inflammation from ramping up too high and causing tissue damage through oxidative stress, Dilger explained.

However, eimeria tricks chickens into over-producing IL-10 earlier than expected, before the immune system can produce enough cytokines to effectively attack the invader. “It’s like the parasite is saying, ‘Everything’s fine. I’m not actually here!’ It’s really trying to evade the immune response,” Dilger said.

To reverse that effect, doctoral student Muhammed Shameer Abdul Rasheed included a novel feed ingredient, a dried egg product with IL-10 antibody activity, in the diet of broiler chickens before inducing coccidiosis.

“We want the bird to have an acute pro-inflammatory response in order to clear the parasite, and that response is dampened when the parasite tricks the bird into overproducing IL-10 antibody. We’re trying to take away the parasite’s ability to manipulate the bird’s own immune system against itself,” Rasheed said.

The IL-10 dried egg product has been shown to be effective against mild eimeria infection in other studies, but it hadn’t been tested in severe cases and in the absence of vaccine administration.

“Our results suggested that dietary dried egg product could be beneficial in promoting gut health during severe infection for particular strains of the parasite, even though suppression of the IL-10 response may promote an exaggerated inflammatory reaction in the intestinal epithelium, which may cause subsequent tissue damage,” Dilger added.

Uncontrolled inflammatory responses can lead to oxidative stress, where chemicals with unpaired electrons, known as free radicals, start to damage healthy tissue. When Rasheed saw the intestinal damage in this study, he decided to test the combined effects of the IL-10 antibody and an antioxidant known as methylsulfonylmethane (MSM). He had previously tested MSM in chickens and found it had no adverse effects on health or growth, but it had never been tried as a treatment for oxidative stress during coccidiosis.

“The IL-10 antibody works to combat the infection through an immune mechanism, which may inadvertently cause oxidative stress, so MSM was used in combination to specifically combat that tissue damage,” Rasheed said. “So, the hypothesis was that if these two interventions are working through different mechanisms, combining them together may actually give us a better response than either of them alone.”

When the research team fed infected birds a combination of MSM and IL-10 antibody, the treatment showed promise. First, chickens that got the treatment showed greater bodyweight gain 7-14 days post-infection than birds that didn’t consume the dietary products. Also, total antioxidant capacity, an overall indicator of how well an animal can counteract oxidative stress, remained higher in treated birds three and four weeks after infection, suggesting lasting dietary effects, the researchers said.

“In the end, the birds still got sick; they still had an infection that reduced their growth for a certain amount of time. Just like with some pharmaceutical agents designed to lessen the effects of the flu in humans, it’s not actually going to prevent you from getting the disease in the first place. However, our goal is to shorten the length of time you’re sick,” Dilger said. “That’s just as meaningful for broiler chickens.”

Dilger said he thinks the dietary interventions may be even more effective in real-world production settings. In the clean, controlled environment of a laboratory study, these broiler chickens were raised on wire flooring to separate the birds from their excrement. However, broiler chickens raised on a commercial farm would be raised on the floor, in direct contact with litter, which is partly how the eimeria infection cycle continues. In the end, the nutritional strategies studied here may act as a kind of insurance for producers to help birds bounce back sooner.

“Producers may not have coccidiosis when they mix this in the feed, but by the time the chickens consume it, the disease may have reared up again. So, if the product is already there, you have some protection,” Dilger said. “Again, it’s not going to prevent the birds from getting coccidiosis, but hopefully it can reduce the untoward effects and allow them to get back to a healthy state faster and continue growing, such that they can remain productive during that time. It’s another important tool in the arsenal for producers.”

The articles, “Dietary supplementation with anti-IL-10 antibody during a severe Eimeria challenge in broiler chickens” and “Effects of methylsulfonylmethane and neutralizing anti- IL-10 antibody supplementation during a mild Eimeria challenge infection in broiler chickens” were published in Poultry Science. M.S. Abdul Rasheed is first author on both articles, and Elanco Animal Health sponsored both studies.

Children's immune response more effective against COVID-19 -- ScienceDaily

Boosting chickens’ own immune response could curb disease — ScienceDaily

  • October 8, 2020

Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks. Various approaches, developed over decades, have been used to control coccidiosis, but the disease remains widespread.

Recent research from the University of Illinois supports the use of immunomodulatory and antioxidant feed additives to reduce the effects of coccidiosis.

“In the last two decades, partially to get around the parasite’s resistance to pharmaceuticals, vaccination has become more prevalent. That’s when I got interested, because nutrition is a key element in the effectiveness of vaccines. Diet and health go together in that way,” says Ryan Dilger, associate professor in the Department of Animal Sciences at Illinois and principal investigator on the research. “So, what we’re talking about here is not a vaccine. Instead, we used nutritional technologies to disrupt the normal reproductive cycle of the parasite.”

When a chicken picks up the parasite, of which there are seven major Eimeria species affecting broilers, its body mounts an immune response, starting with a cascade of inflammatory proteins known as cytokines. These cause the bird to stop eating and rest, so the immune system can do its work. In normal disease progression, an anti-inflammatory mediator known as interleukin-10 (IL-10) is eventually produced to keep the inflammation from ramping up too high and causing tissue damage through oxidative stress.

However, Eimeria tricks chickens into over-producing IL-10 earlier than expected, before the immune system can produce enough cytokines to effectively attack the invader. “It’s like the parasite is saying, ‘Everything’s fine. I’m not actually here!’ It’s really trying to evade the immune response,” Dilger says.

To reverse that effect, doctoral student Muhammed Shameer Abdul Rasheed included a novel feed ingredient, a dried egg product with IL-10 antibody activity, in the diet of broiler chickens before inducing coccidiosis.

“We want the bird to have an acute pro-inflammatory response in order to clear the parasite, and that response is dampened when the parasite tricks the bird into overproducing IL-10 antibody. We’re trying to take away the parasite’s ability to manipulate the bird’s own immune system against itself,” Rasheed says.

The IL-10 dried egg product has been shown to be effective against mild Eimeria infection in other studies, but it hadn’t been tested in severe cases and in the absence of vaccine administration.

“Our results suggested that dietary dried egg product could be beneficial in promoting gut health during severe infection for particular strains of the parasite, even though suppression of the IL-10 response may promote an exaggerated inflammatory reaction in the intestinal epithelium, which may cause subsequent tissue damage,” Dilger says.

Uncontrolled inflammatory responses can lead to oxidative stress, where chemicals with unpaired electrons, known as free radicals, start to damage healthy tissue. When Rasheed saw the intestinal damage in this study, he decided to test the combined effects of the IL-10 antibody and an antioxidant known as methylsulfonylmethane or MSM. He had previously tested MSM in chickens and found it had no adverse effects on health or growth, but it had never been tried as a treatment for oxidative stress during coccidiosis.

“The IL-10 antibody works to combat the infection through an immune mechanism, which may inadvertently cause oxidative stress, so MSM was used in combination to specifically combat that tissue damage,” Rasheed says. “So the hypothesis was that if these two interventions are working through different mechanisms, combining them together may actually give us a better response than either of them alone.”

When the research team fed infected birds a combination of MSM and IL-10 antibody, the treatment showed promise. First, chickens that got the treatment showed greater body weight gain 7-14 days post-infection than birds that didn’t consume the dietary products. Also, total antioxidant capacity, an overall indicator of how well an animal can counteract oxidative stress, remained higher in treated birds three and four weeks after infection, suggesting lasting dietary effects.

“In the end, the birds still got sick; they still had an infection that reduced their growth for a certain amount of time. Just like with some pharmaceutical agents designed to lessen the effects of the flu in humans, it’s not actually going to prevent you from getting the disease in the first place. However, our goal is to shorten the length of time you’re sick,” Dilger says. “That’s just as meaningful for broiler chickens.”

Dilger thinks the dietary interventions may be even more effective in real-world production settings. In the clean, controlled environment of a laboratory study, these broiler chickens were raised on wire flooring to separate the birds from their excrement. However, broiler chickens raised on a commercial farm would be raised on the floor, in direct contact with litter, which is partly how the Eimeria infection cycle continues. In the end, the nutritional strategies studied here may act as a kind of insurance for producers to help birds bounce back sooner.

“Producers may not have coccidiosis when they mix this in the feed, but by the time the chickens consume it, the disease may have reared up again. So if the product is already there, you have some protection,” Dilger says. “Again, it’s not going to prevent the birds from getting coccidiosis, but hopefully it can reduce the untoward effects and allow them to get back to a healthy state faster and continue growing, such that they can remain productive during that time. It’s another important tool in the arsenal for producers.”

New therapy extends breast cancer survival rate, prevents reoccurrence

Boosting chickens’ own immune response could curb disease

  • October 7, 2020

URBANA, Ill. – Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks. Various approaches, developed over decades, have been used to control coccidiosis, but the disease remains widespread.

Recent research from the University of Illinois supports the use of immunomodulatory and antioxidant feed additives to reduce the effects of coccidiosis.

“In the last two decades, partially to get around the parasite’s resistance to pharmaceuticals, vaccination has become more prevalent. That’s when I got interested, because nutrition is a key element in the effectiveness of vaccines. Diet and health go together in that way,” says Ryan Dilger, associate professor in the Department of Animal Sciences at Illinois and principal investigator on the research. “So, what we’re talking about here is not a vaccine. Instead, we used nutritional technologies to disrupt the normal reproductive cycle of the parasite.”

When a chicken picks up the parasite, of which there are seven major Eimeria species affecting broilers, its body mounts an immune response, starting with a cascade of inflammatory proteins known as cytokines. These cause the bird to stop eating and rest, so the immune system can do its work. In normal disease progression, an anti-inflammatory mediator known as interleukin-10 (IL-10) is eventually produced to keep the inflammation from ramping up too high and causing tissue damage through oxidative stress.

However, Eimeria tricks chickens into over-producing IL-10 earlier than expected, before the immune system can produce enough cytokines to effectively attack the invader. “It’s like the parasite is saying, ‘Everything’s fine. I’m not actually here!’ It’s really trying to evade the immune response,” Dilger says.

To reverse that effect, doctoral student Muhammed Shameer Abdul Rasheed included a novel feed ingredient, a dried egg product with IL-10 antibody activity, in the diet of broiler chickens before inducing coccidiosis.

“We want the bird to have an acute pro-inflammatory response in order to clear the parasite, and that response is dampened when the parasite tricks the bird into overproducing IL-10 antibody. We’re trying to take away the parasite’s ability to manipulate the bird’s own immune system against itself,” Rasheed says.

The IL-10 dried egg product has been shown to be effective against mild Eimeria infection in other studies, but it hadn’t been tested in severe cases and in the absence of vaccine administration.

“Our results suggested that dietary dried egg product could be beneficial in promoting gut health during severe infection for particular strains of the parasite, even though suppression of the IL-10 response may promote an exaggerated inflammatory reaction in the intestinal epithelium, which may cause subsequent tissue damage,” Dilger says.

Uncontrolled inflammatory responses can lead to oxidative stress, where chemicals with unpaired electrons, known as free radicals, start to damage healthy tissue. When Rasheed saw the intestinal damage in this study, he decided to test the combined effects of the IL-10 antibody and an antioxidant known as methylsulfonylmethane or MSM. He had previously tested MSM in chickens and found it had no adverse effects on health or growth, but it had never been tried as a treatment for oxidative stress during coccidiosis.

“The IL-10 antibody works to combat the infection through an immune mechanism, which may inadvertently cause oxidative stress, so MSM was used in combination to specifically combat that tissue damage,” Rasheed says. “So the hypothesis was that if these two interventions are working through different mechanisms, combining them together may actually give us a better response than either of them alone.”

When the research team fed infected birds a combination of MSM and IL-10 antibody, the treatment showed promise. First, chickens that got the treatment showed greater body weight gain 7-14 days post-infection than birds that didn’t consume the dietary products. Also, total antioxidant capacity, an overall indicator of how well an animal can counteract oxidative stress, remained higher in treated birds three and four weeks after infection, suggesting lasting dietary effects.

“In the end, the birds still got sick; they still had an infection that reduced their growth for a certain amount of time. Just like with some pharmaceutical agents designed to lessen the effects of the flu in humans, it’s not actually going to prevent you from getting the disease in the first place. However, our goal is to shorten the length of time you’re sick,” Dilger says. “That’s just as meaningful for broiler chickens.”

Dilger thinks the dietary interventions may be even more effective in real-world production settings. In the clean, controlled environment of a laboratory study, these broiler chickens were raised on wire flooring to separate the birds from their excrement. However, broiler chickens raised on a commercial farm would be raised on the floor, in direct contact with litter, which is partly how the Eimeria infection cycle continues. In the end, the nutritional strategies studied here may act as a kind of insurance for producers to help birds bounce back sooner.

“Producers may not have coccidiosis when they mix this in the feed, but by the time the chickens consume it, the disease may have reared up again. So if the product is already there, you have some protection,” Dilger says. “Again, it’s not going to prevent the birds from getting coccidiosis, but hopefully it can reduce the untoward effects and allow them to get back to a healthy state faster and continue growing, such that they can remain productive during that time. It’s another important tool in the arsenal for producers.”

###

The articles, “Dietary supplementation with anti-IL-10 antibody during a severe Eimeria challenge in broiler chickens” [DOI: 10.1016/j.psj.2020.09.012] and “Effects of methylsulfonylmethane and neutralizing anti- IL-10 antibody supplementation during a mild Eimeria challenge infection in broiler chickens” [DOI: 10.1016/j.psj.2020.09.046] are published in Poultry Science. M.S. Abdul Rasheed is first author on both articles, and Elanco Animal Health sponsored both studies.

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.

Trump’s Covid-19 Treatment Seeks to Boost Immune Response

Trump’s Covid-19 Treatment Seeks to Boost Immune Response

  • October 5, 2020

The experimental infusion doctors have given to President Trump seeks to counter a problem affecting many older Covid-19 patients: an ineffective immune response.

Among other treatments, Mr. Trump has taken a drug cocktail from

Regeneron Pharmaceuticals Inc.


REGN 5.69%

that hasn’t been approved for broad use but aims to jump-start an immune defense by supplying antibodies to help fight the coronavirus that causes Covid-19. The company says its results suggest the infusion can help people infected with the coronavirus who haven’t yet produced their own antibodies.

The approach makes sense in elderly patients, whose bodies are often less able to fight off pathogens, said Janko Nikolich-Zugich, an immunologist and gerontologist who is a professor at the University of Arizona. “You don’t control the virus as quickly as you should” with older patients, he said.

A growing body of research points to the immune system as a key reason why the elderly are so susceptible to serious cases of Covid-19. As a person ages, the system undergoes “immunosenescence,” gradually losing its ability to mount a response to infection as robustly as it once did. The complicated mechanisms of the immune system don’t work together as well, leading to a slower and less-powerful defense.

In addition to his age, 74, Mr. Trump’s weight also may raise concerns about his immunity, as obesity has been tied to impaired response. And a study published in the journal Nature this August also highlighted the possibility that older men, in particular, might tend to mount a less-robust immune response to the virus.

The President’s Medical Treatment

About 80% of deaths in the U.S. have been among those 65 and older, and about 31% of deaths are among people aged at least 85 years, according to death-certificate data from the Centers for Disease Control and Prevention. This is partly because the elderly are often frailer, and they also have higher rates of conditions such as heart disease and diabetes that are risk factors for severe impact from Covid-19.

But their immune systems are another important factor, researchers say. “When you challenge a body with a virus or a vaccine, there’s just not the vigorous response,” said Cari Levy, a geriatrician who is a professor at the University of Colorado.

Older people often produce fewer, and less-effective, antibodies. These y-shaped proteins are supposed to bind to invading pathogens, neutralizing them and signaling to the body to destroy them.

“It’s slower, it’s unreliable—you probably don’t make as many” antibodies, said Peter Chin-Hong, a professor of medicine at the University of California, San Francisco. The hope is that treatments like Regeneron’s experimental cocktail might help fill that gap early in the infection process, potentially slowing the initial spread of the virus.

Elderly immune systems also often have problems generating the powerful soldiers known as T-cells, which supply a main line of defense against invaders. Production of these cells, from a gland in the chest known as the thymus, drops sharply over the course of a person’s life. They can also lose some of their function.

One recent study suggests that older men have a harder time getting their T-cells into action. New research published this August in Nature looked at 98 patients infected with the coronavirus and found evidence that the immune response varied by gender.

“Especially men of older age were very impaired with respect to T-cell activation,” said Akiko Iwasaki, a professor of immunobiology at Yale University who led the study. Those men who had the least T-cell response tended to have worse Covid-19 outcomes, she said.

There is no treatment currently available that would help with Covid-19 patients’ T-cells, she said. Potentially a future vaccine might do this, but vaccines are often less effective in older patients.

But even as vital parts of an elderly person’s immune system are performing sluggishly, another response can cause trouble by firing up too much. As the body fails to contain the virus quickly, the immune system may produce too many of a type of protein called cytokines. These can damage blood vessels and allow fluid to seep into the lungs.

It isn’t clear why this “cytokine storm” effect is triggered in some patients but not others. But elderly people tend to have a higher level of inflammation, and cytokines, said Amber Mueller, a molecular biologist who is a postdoctoral research fellow at Harvard Medical School.

This greater baseline level of inflammation is one reason the soldier T-cells are less effective, and it sets the stage for the dangerous overproduction of cytokines, she said.

President Trump remained hospitalized early Monday, after doctors offered conflicting signals about how he is faring with Covid-19. The president sought to project confidence and vigor over the weekend.

Write to Anna Wilde Mathews at anna.mathews@wsj.com

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Bharat Biotech’s Covaxin is one of three vaccines that are currently in human trials in India.

Bharat Biotech signs pact for adjuvant to boost Covaxin’s immune response

  • October 5, 2020

NEW DELHI :
Bharat Biotech International Ltd will use adjuvant Alhydroxiquim-II to boost immune response and provide longer lasting immunity for its novel coronavirus vaccine candidate Covaxin, the company said in statement on Monday. The adjuvant is being used under a licensing agreement signed with US-based ViroVax LLC.

An adjuvant is a substance that is added to a vaccine to boost production of antibodies and provide immunity for a longer time, which in turn reduces the dose of antigen needed for vaccination.

“Our partnership with ViroVax resonates with Bharat Biotech’s relentless efforts towards developing safe and effective vaccines coupled with long term immunity,” Bharat Biotech chairman and managing director Krishna Ella said.

ViroVax is supported by funding from the US’ National Institute of Allergy and Infectious Diseases (NIAID), that is among the agencies leading the covid-19 response in the US.

Covaxin is an inactivated vaccine derived from a strain of SARS-CoV2 virus, isolated at the Indian Council of Medical Research’s National Institute of Virology (NIV) at Pune.

Bharat Biotech is currently conducting Phase II human trials of Covaxin after receiving approval from the Drug Controller General of India (DCGI) V.G. Somani. The company is aiming to produce around 200 million doses of covid-19 vaccine at its Hyderabad facility once it receives regulatory approval.

Ella said that the Alhydroxiquim-II adjuvant is different from an adjuvant like aluminium hydroxide, which is the commonly used adjuvant for covid-19 vaccines, as it induces a Th1 based response and not a Th2 based response that has a theoretical risk of vaccine associated enhanced respiratory diseases.

A Th1 response is aimed at increased cell-mediated immunity against the disease, which primarily involves secretion of immune system cells to an infection or accumulating damaged or dead cells. On the other hand, Th2 response leads to humoral immunity, that leads to secretion of antibodies.

Bharat Biotech’s Covaxin is one of three vaccines that are currently in human trials in India, with the other two being Serum Institute of India’s Covishield, co-developed by University of Oxford and UK’s Astrazeneca plc, and Zydus Cadila’s indigenous vaccine ZyCoV-D.

On Sunday, Union health minister Harsh Vardhan said that the government is aiming to vaccinate roughly 200-250 million people in India with around 400-500 million doses by July 2021.

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Researchers start to unravel immune system’s complex response to COVID

Researchers start to unravel immune system’s complex response to COVID

  • October 2, 2020

One of COVID-19’s scariest mysteries is why some people are mildly ill or have no symptoms and others rapidly die — and scientists are starting to understand why.

An international team of researchers found that in some people with severe COVID-19, the body goes rogue and attacks one of its own key immune defenses instead of fighting the coronavirus. Most were men, helping to explain why the virus is hitting men harder than women.

And separate research suggests that many children fare better than adults thanks to robust “first responder” immune cells that wane with age.

They’re the latest in a list of studies uncovering multiple features of the immune system’s intricate cascade that can tip the scales between a good or bad outcome. Next up: Figuring out if all these new clues might offer much-needed ways to intervene.

“We have the knowledge and capability of really boosting many aspects of the immune system. But we need to not use the sledge hammer,” cautioned Dr. Betsy Herold of New York’s Albert Einstein College of Medicine, who co-authored the child study.

Adding to the complexity, people’s wildly varying reactions also reflect other factors, such as how healthy they were to begin with and how much of the virus — the “dose” — they were exposed to.

“Infection and what happens after infection is a very dynamic thing,” said Alessandro Sette, a researcher at the La Jolla Institute for Immunology in San Diego, who is studying yet another piece of the immune response.

Immune primer

There are two main arms of the immune system. Innate immunity is the body’s first line of defense. As soon as the body detects a foreign intruder, key molecules, such as interferons and inflammation-causing cytokines, launch a wide-ranging attack.

Innate immune cells also alert the slower-acting “adaptive” arm of the immune system, the germ-specific sharpshooters, to gear up. B cells start producing virus-fighting antibodies, the proteins getting so much attention in the vaccine hunt.

But antibodies aren’t the whole story. Adaptive immunity’s many other ingredients include “killer” T cells that destroy virus-infected cells — and “memory” T and B cells that remember an infection so they spring into action quicker if they encounter that germ again.

A missing piece

Usually when a virus invades a cell, proteins called Type I interferons spring into action, defending the cell by interfering with viral growth. But new research shows those crucial molecules were essentially absent in a subset of people with severe COVID-19.

An international project uncovered two reasons. In blood from nearly 1,000 severe COVID-19 patients, researchers found 1 in 10 had what are called auto-antibodies — antibodies that mistakenly attack those needed virus fighters. Especially surprising, autoimmune disorders tend to be more common in women — but 95% of these COVID-19 patients were men.

The researchers didn’t find the damaging molecules in patients with mild or asymptomatic COVID-19.

In another 660 severely ill patients, the same team found 3.5% had gene mutations that didn’t produce Type I interferons.

Each of those silent vulnerabilities was enough to tip the balance in favor of the virus early on, said Dr. Jean-Laurent Casanova, an infectious disease geneticist at Rockefeller University in New York, who co-leads the COVID Human Genetic Effort. He is paid by the Howard Hughes Medical Institute, which also helps fund The Associated Press Health and Science Department.

Certain interferons are used as medicines and are under study as a possible COVID-19 treatment; the auto-antibody discovery adds another factor to consider.

Kids’ immunity revs fast

It’s not clear why children in general appear less at risk from COVID-19. But occasionally they’re sick enough for hospitalization, giving Herold’s team the opportunity to compare 60 adults and 65 children and teens at New York’s Montefiore Health System.

The children produced much higher levels of certain cytokines that are among the innate immune system’s first responders. When the immune system’s next stage kicked in, both adults and children made antibodies targeting the coronavirus. Here’s the rub: The adults’ adaptive immune response was more the type that can trigger an inflammatory overreaction.

The findings suggest kids’ early robust reaction lets their immune system get ahead of the virus, making an overreaction less likely “and that’s protecting them,” Herold said.

Any preexisting immunity?

The coronavirus that causes COVID-19 is new to humans. But Sette’s team studied blood samples that were stored in freezers before the pandemic and found some harbored memory T cells that recognized a tiny portion of the new virus in laboratory tests.

“You can actually tell that this is an experienced T cell. This has seen combat before,” Sette said. Researchers in Germany, Britain and other countries have made similar findings.

The new coronavirus has cousins that cause as many as 30% of common colds, so researchers believe those T cells could be remnants from past colds.

But despite the speculation, “we don’t know yet” that having those T cells makes any difference in who gets seriously sick with COVID-19, noted Rory de Vries, co-author of a study in the Netherlands that also found such T cells in old blood.

All these findings beg for a deeper understanding of the myriad ways some people can be more susceptible than others.

“We need to look quite broadly and not jump into premature conclusions about any one particular facet of the immune system,” said Stanford University immunologist Bali Pulendran. He also has found some innate immune cells “in a state of hibernation” in seriously ill adults and next is looking for differences before and after people get sick.

But, “it’s not just all about the immune system,” cautioned Dr. Anita McElroy, a viral immunity expert at the University of Pittsburgh who’s closely watching the research. A way to tell in advance who’s most at risk? “We’re a long, long way from that.”

NOTE: The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.

Children's immune response more effective against COVID-19 -- ScienceDaily

Cells sacrifice themselves to boost immune response to viruses — ScienceDaily

  • October 2, 2020

Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection. New research appearing in the journal Nature Immunology describes how different cells in the immune system work together, communicate, and — in the case of cells called neutrophils — bring about their own death to help fight off infections. The findings could have important implications for the development of vaccines and anti-viral therapies.

“The immune system consists of several different types of cells, all acting in coordination,” said Minsoo Kim, Ph.D., a professor of Microbiology and Immunology at the University of Rochester Medical Center (URMC) and senior author of the study. “These findings show that cells called neutrophils play an important altruistic role that benefits other immune cells by providing key resources for their survival and, in the process, enhancing the body’s immune response against a virus.”

Neutrophils are a key component of the innate immune system, the part of the body’s defenses that is always switched on and alert for bacterial and viral invaders. The vast majority of white cells circulating in blood are neutrophils and, as a result, these cells are the first on the scene to respond to an infection.

However, neutrophils are not fully equipped to eliminate a viral threat by themselves. Instead, when the respiratory tract is infected with a virus like influenza or COVID-19, a large number of neutrophils rush to the infection site and release chemical signals. This triggers the production of specialized T cells, which are part of the body’s adaptive immune system, which is activated to produce a more direct response to specific infections. Once mobilized in sufficient quantities, a process that typically takes several days, these T cells target and ultimately destroy the infected cells.

The new study, which was conducted in mice infected with the flu virus, shows that in addition to jump-starting the adaptive immune response, neutrophils have one more important mission that requires that they sacrifice themselves. As T cells arrive at the infection site, the neutrophils initiate a process called apoptosis, or controlled death, which releases large quantities of a molecule called epidermal growth factor (EGF). EGF provides T cells with the extra boost in energy necessary to finish the job.

“This study represents an important paradigm shift and shows that the adaptive immune system doesn’t generate a successful response without instruction and help from the innate immune system,” said Kim. “The findings reveal, for the first time, how different immune cells work together, and even sacrifice themselves, to accomplish the same goal of protecting the host from the viral infection.”

Kim and his colleagues point out that this new understanding of how the immune system functions opens the door to potential new methods to intervene and optimize the collaboration between different immune cells during viral infection. These efforts could ultimately lead to more effective vaccines and anti-viral therapies for respiratory infections like the flu and coronavirus.

Story Source:

Materials provided by University of Rochester Medical Center. Original written by Mark Michaud. Note: Content may be edited for style and length.

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