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Vaxzevria Vaccine Boosts Mucosal Immunity In COVID-19 Recovered
In a recent study published in Immunology & Cell Biology, scientists examine the protective efficacy of coronavirus disease 2019 (COVID-19) vaccine-induced mucosal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs).
Study: Mucosal antibody responses following Vaxzevria vaccination. Image Credit: ANDRES MENA PHOTOS / Shutterstock.Com
Mucosal linings in the eyes, nose, mouth, and throat act as the first line of defense against invading respiratory pathogens, such as SARS-CoV-2. Previous studies have indicated that SARS-CoV-2 spike protein-specific mucosal immunoglobulin A (IgA) antibodies can provide strong protection against breakthrough COVID-19 infections and novel viral variants.
Intramuscularly-administered adenoviral vector-based COVID-19 vaccines have been shown to induce weak mucosal immune responses in infection-naïve individuals. In this context, a recent study reported that the adenoviral vector-based COVID-19 vaccine Vaxzevria induces higher levels of mucosal IgG and IgA antibodies in COVID-19-recovered individuals compared to infection-naïve individuals.
In the current study, scientists compare plasma and mucosal antibody levels from saliva and tear samples, respectively. The ability of these antibodies to induce Fc effector functions and cross-react with SARS-CoV-2 variants among Vaxzevria-vaccinated individuals with or without prior SARS-CoV-2 infection was also determined. Furthermore, the researchers evaluated how viral exposure impacts mucosal antibody responses after Vaxzevria vaccination.
Important observationsCOVID-19-recovered individuals exhibited IgG responses in both saliva and plasma samples after a single dose of the Vaxzevria vaccine as compared to infection-naïve individuals who received two vaccine doses. Moreover, COVID-19-recovered individuals exhibited significantly higher spike-specific engagements of Fc-receptors and spike-specific salivary IgA1 responses after the first vaccine dose.
The salivary and plasma antibody response and Fc receptor engagement in COVID-19-recovered individuals after the second vaccination failed to reach the levels observed two weeks after the first vaccine dose. However, the antibody levels and Fc receptor engagement in saliva after the second vaccine dose remained significantly higher than the pre-vaccination responses against SARS-CoV-2 VOC spike antigens.
Unlike vaccinated COVID-19-recovered individuals, infection-naïve vaccinated individuals exhibited weak salivary and plasma antibody responses after the first and second vaccinations. However, these individuals exhibited significant induction in plasma IgG and Fc engagement responses after receiving a third booster dose of a messenger ribonucleic acid (mRNA) COVID-19 vaccine. Nevertheless, this booster dose caused only modest changes in salivary antibody response in these individuals.
Overall, these findings indicate that salivary IgA and antibody-mediated Fc receptor engagement responses decline after a second vaccine dose in COVID-19-recovered individuals. This highlights the need for booster doses capable of inducing robust anti-SARS-CoV-2 mucosal immunity.
Neutralizing antibody response at mucosaThe virus neutralization assay findings revealed that both the first and second COVID-19 vaccinations could not induce a sufficient salivary neutralizing response in most of the COVID-19-recovered individuals.
In contrast, COVID-19 recovered and infection-naïve individuals exhibited broad neutralizing responses in plasma against SARS-CoV-2 VOCs after first and booster vaccination, respectively.
COVID-19-recovered individuals exhibited mucosal antibody-mediated Fc receptor engagement responses against a wide range of SARS-CoV-2 VOCs after vaccination. However, this response was primarily targeted against the wild-type SARS-CoV-2 strain, with weaker recognition of more recent Omicron variants.
Salivary IgAs, rather than plasma IgA, were cross-reactive across a broad range of SARS-CoV-2 VOCs in COVID-19-recovered individuals, particularly after the first vaccination. Thus, the induction of cross-reactive IgA at the mucosa is crucial for developing protection against newly emerging viral variants.
Interestingly, our findings show that IgG antibodies in the bloodstream can mostly recognize the original virus, while mucosal IgA antibodies is able to target both the ancestral virus and the newer variants."
Study significanceIntramuscularly-delivered Vaxzevria vaccine can effectively induce both systemic and mucosal antibody responses in COVID-19-recovered individuals. Moreover, the study findings indicate that IgG-mediated mucosal responses are largely non-neutralizing and specific to the wild-type strain of SARS-CoV-2 and, as a result, do not provide sufficient protection against breakthrough infections. In contrast, vaccine-induced, highly cross-reactive mucosal IgA response can effectively provide protection against newly emerging viral variants.
These results indicate that previous exposure to SARS-CoV-2 through the mucosal route may be necessary to improve localized antibody protection at the mucosal surfaces."
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WHO Recommends Dropping Component Of Many Flu Vaccines
The World Health Organization has recommended dropping a component of many flu vaccines because the viruses it protects against appear to have been driven into extinction in the Covid-19 pandemic.
A family of viruses known as influenza B/Yamagata has not been seen since March 2020, when flu circulation worldwide declined to very low levels in the face of the onslaught of Covid and the protections people took to avoid contracting it. Flu transmission eventually resumed, but of the tens of thousands of influenza B viruses detected and subtyped in the years since, B/Yamagata viruses have not been seen.
"Right now there really isn't any benefit to having Yamagata in the vaccine," said David Wentworth, director of the WHO's Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza at the Centers for Disease Control and Prevention, who was on the expert panel that made the recommendation.
The decision was applauded by influenza virologist Florian Krammer, of Mount Sinai School of Medicine in Manhattan. "Why would you include something that's not around?" he asked.
The recommendation was made following a weeklong meeting of flu experts from around the world who gather twice a year at the WHO to study circulating flu viruses to advise on what future versions of flu shots should protect against. This week's meeting was to recommend what viruses should go into the 2024 Southern Hemisphere's winter shot.
In addition to the fact that there is no benefit to including B/Yamagata viruses in the vaccine at this point, there is a theoretical risk of doing so, a report from the meeting noted. Manufacturers must grow B/Yamagata viruses for inclusion in the vaccines. In most flu shots — the types that are injected — those viruses are killed at a point in the manufacturing process. But a leak from a manufacturing plant could theoretically release B/Yamagata viruses into the world. Likewise, the intranasal flu vaccine FluMist — made by AstraZeneca — contains live but weakened flu viruses. Those viruses, too, could theoretically reintroduce the virus family to the world.
The committee urged regulatory bodies to work with flu vaccine manufacturers to remove the B/Yamagata component from vaccine formulation "as soon as possible."
"Here we're balancing the absence of circulation of the B/Yamagata lineage virus with a theoretical risk that we are manufacturing and using a component that's not necessary," said Kanta Subbarao, director of the WHO's Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia.
B/Yamagata viruses haven't been seen since late March 2020. The rapid and global implementation of social distancing measures, masking, and the profound early reduction in international travel resulted in a substantial reduction in flu transmission. There was virtually no flu season in the winter of 2020-21.
"The other ones — H1, H3, and Victoria — made it through. But there was also a huge bottleneck and Yamagata was not lucky enough to make it through," said Krammer.
For many low- and middle-income countries, the recommendation will not lead to any change. Many still use trivalent vaccine — a three-in-one shot that protects against influenza A viruses H1N1 and H3N2, plus one of the flu B viruses. In recent years, that would have been the B/Victoria lineage, the only B viruses still circulating.
In countries that moved to quadrivalent flu vaccines a number of years ago, the recommendation may lead to changes in flu vaccine manufacturing, but it won't be immediate, the experts warned at a press conference the WHO called to announce the outcome of the week's discussions. Changing the composition of a vaccine requires regulatory approval, which in the case of the United States means signoff from the Food and Drug Administration.
Wentworth said the FDA has been discussing the possibility of recommending removal of the B/Yamagata component from flu vaccines. But whether that's easy or difficult to do will depend on whether flu vaccine manufacturers still have licenses for former trivalent formulations. STAT reached out to the FDA for comment on the issue, but has not yet heard back.
"Basically it's going to be different between different companies — whether or not they retained their trivalent license and in which form it was retained, and whether their processes have changed, even though they have their old license," Wentworth said. "It's not something that you can do in one day. It's going to take time. And that's why our suggestion was to really forecast to the manufacturers and the regulatory authorities that they can start working on this process and try to expedite the process where it makes sense, for safety, etc."
The experts stressed there is no disadvantage to individuals of getting a quadrivalent vaccine at this point, but no advantage from the B/Yamagata component either.
The flu shots currently used in the United States employ a quadrivalent formulation.
In the years since the Yamagata viruses ceased to be detected, there has been active discussion in the scientific community about replacing that component of quadrivalent shots with another type of flu virus — a second H3N2 vaccine, or one of the bird or swine flu viruses that are seen as pandemic threats. While those ideas are still possibilities, that idea is not yet ready for prime time, Subbarao said.
"From a regulatory standpoint, that's not very straightforward," she said. "I think there is a great interest from the influenza research community, but it is still at the research stage rather than being ready for the kinds of discussions that our committee has to make recommendations for the vaccine composition."
Inactivated Poliovirus Vaccine Elicits Persistent Immunity For Up To 10 Years
In a recent article published in eClinicalMedicine, researchers evaluated the immune or neutralizing antibodies (nAb) persistence of the Sabin strain-derived inactivated poliovirus vaccine (sIPV) compared to wild poliovirus seed strains (wIPV) against currently circulating and wild poliovirus strains.
Study: Immune persistence of an inactivated poliovirus vaccine derived from the Sabin strain: a 10-year follow-up of a phase 3 study. Image Credit: Smile Studio AP/Shutterstock.Com Background Poliomyelitis virus typically infects children below five years; thus, repeated oral poliovirus vaccine (OPV) administration occurs in this time frame. However, since OPV can cause vaccine-associated paralytic poliomyelitis (VAPP), IPV might be a better alternative to protect infants against polioviruses.
In a previous phase III clinical trial of sIPV in China, researchers demonstrated the potency of its three-dose primary vaccination in two-, three-, and four-month-old infants. Its booster dose increased the geometric mean titers (GMTs) of nAbs against polioviruses type 1/2/3 in 18-month-old children.
Even though sIPV-induced nAbs conferred protection for a minimum of 10 years after the booster dose, it was still inferior to those induced by wIPV-based IPV. Moreover, the persistence of these nAbs after completion of sIPV primary and booster regimens is unclear. Thus, sIPV requires further validation in large-scale population vaccination trials.
About the studyIn the present study, researchers evaluated nAb titers in serum samples of children from Pingle County in GuanXi Province of China who had completed the primary and booster regimens of sIPV (or wIPV) between January 1, 2012, and August 31, 2014, during a previous phase III clinical trial.
Children participating in this study were 4-, 6-, 8-, and 10-year-olds. While 170 children formed the sIPV group, there were 169 children in the control wIPV group.
After receiving their prime-boost vaccine regimen, which they did by 18 months of age, 287, 262, 237, and 207 children provided their serum samples. The team used these samples from the sIPV and wIPV groups to analyze protective rates and GMTs of nAbs against poliovirus types 1/2/3. In addition, they detected nAbs against attenuated Sabin strains to determine immune persistence.
Specifically, the researchers used a microneutralization assay to determine titers of nAbs against polioviruses 1/2/3. They presented protective rates as percentages with 95% confidence intervals (95% CIs) and converted nAb titers to log2 titers to calculate GMTs and 95% CIs. Furthermore, the team computed reduction times of GMTs as GMTs at 30 days post-boosting divided by GMTs at 4, 6, 8, or 10 years old.
Finally, based on data distribution characteristics, they chose the Mann–Whitney U, independent-samples t, or Fisher's exact tests to examine intergroup variations.
ResultsDuring 10 years of follow-up, the protective rates and nAb titers against poliovirus types 1/2/3 induced by sIPV versus wIPV were numerically similar, suggesting these nAbs showed adequate persistence; thus, sIPV could be an alternative or substitute for OPV. However, GMTs of nAbs against poliovirus types 1/2/3 varied for sIPV and wIPV groups from the time of receiving booster shot to 10 years of age, except for poliovirus type 3 in four-year-olds.
Further analyses uncovered that at four years after booster vaccination, the GMTs of nAbs against poliovirus types 1/2/3 decreased between 80.5%–91.8% in the sIPV group and 82.3%–89.0% in the wIPV group.
However, during the age of 6–10 years, the decrease in GMTs slowed for poliovirus types 1/2/3 in both groups. The GMTs of poliovirus types 1/2/3 in both groups persisted at 1:8 till 10 years of age in both groups.
ConclusionsBoth sIPV and wIPV induced persistent immunity of at least 10 years after a three-dose vaccination series, suggesting the feasibility of using attenuated Sabin strains to prepare inactivated poliovirus vaccines.
In the postpolio era, vaccines with high immune persistence, such as sIPV, could be critical for eradicating poliomyelitis in developing nations.
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