Nature
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Observational Study
SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses.
This reassuring study published in Nature by researchers from Wash U Med investigated persisting COVID immunity following the Pfizer mRNA vaccination (BNT162b2). Turner et al. looked at the presence of not only circulating antibody-secreting B cells, but also germinal centre B cells found in the axillary lymph nodes of 14 study volunteers.
While the persistence of mRNA-vaccine induced immunity to SARS-CoV-2 has already been demonstrated to last at least 6 months, and likely 12 months, we just do not yet have the data to know if or when vaccine boosters will be required beyond that.
Turner's study is particularly exciting because they found spike-protein binding B cells in the germinal centre of draining lymph nodes in all 14 post-immunisation participants for the full 15 weeks of the study. The germinal centre response was so vigorous and persistent that the researchers believe this could represent COVID-protection lasting for years.
"Ellebedy said the immune response observed in his team’s study appears so robust and persistent that he thinks that it could last for years. The researcher based his assessment on the fact that germinal centre reactions that persist for several months or longer usually indicate an extremely vigorous immune response that culminates in the production of large numbers of long-lasting immune cells, called memory B cells. Some memory B cells can survive for years or even decades..." – Dr Francis Collins, NIH Directors Blog
This study builds on the same team's earlier work (Turner 2021 May) looking at bone marrow plasma cells in those who have recovered from mild COVID infection, also showing a long-lived immune response.
COVID persistent immunity takeaway:
Although COVID-19 and developed vaccines have been circulating for only 12-18 months, these immune-response studies give some hope that the miracle of mRNA vaccines may not only be in their efficacy, but also in the longevity of protection.
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The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India1-5. Since then, it has become dominant in some regions of India and in the UK, and has spread to many other countries6. The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), which contain diverse mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein that may increase the immune evasion potential of these variants. ⋯ Sera from individuals who had received one dose of the Pfizer or the AstraZeneca vaccine had a barely discernible inhibitory effect on the Delta variant. Administration of two doses of the vaccine generated a neutralizing response in 95% of individuals, with titres three- to fivefold lower against the Delta variant than against the Alpha variant. Thus, the spread of the Delta variant is associated with an escape from antibodies that target non-RBD and RBD epitopes of the spike protein.
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The emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer-BioNTech mRNA vaccine (BNT162b2). ⋯ Consistent with these observations, our single-cell transcriptomics analysis demonstrated an approximately 100-fold increase in the frequency of a myeloid cell cluster enriched in interferon-response transcription factors and reduced in AP-1 transcription factors, after secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and neutralizing antibody responses, and show that a monocyte-related signature correlates with the neutralizing antibody response against the B.1.351 variant. Collectively, these data provide insights into the immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response after booster immunization.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuing to evolve around the world, generating new variants that are of concern on the basis of their potential for altered transmissibility, pathogenicity, and coverage by vaccines and therapeutic agents1-5. Here we show that serum samples taken from twenty human volunteers, two or four weeks after their second dose of the BNT162b2 vaccine, neutralize engineered SARS-CoV-2 with a USA-WA1/2020 genetic background (a virus strain isolated in January 2020) and spike glycoproteins from the recently identified B.1.617.1, B.1.617.2, B.1.618 (all of which were first identified in India) or B.1.525 (first identified in Nigeria) lineages. Geometric mean plaque reduction neutralization titres against the variant viruses-particularly the B.1.617.1 variant-seemed to be lower than the titre against the USA-WA1/2020 virus, but all sera tested neutralized the variant viruses at titres of at least 1:40. The susceptibility of the variant strains to neutralization elicited by the BNT162b2 vaccine supports mass immunization as a central strategy to end the coronavirus disease 2019 (COVID-19) pandemic globally.
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Randomized Controlled Trial Multicenter Study
Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans.
The Ad26. COV2. S vaccine1-3 has demonstrated clinical efficacy against symptomatic COVID-19, including against the B.1.351 variant that is partially resistant to neutralizing antibodies1. ⋯ COV2. S were reduced against the B.1.351 and P.1 variants, but functional non-neutralizing antibody responses and T cell responses were largely preserved against SARS-CoV-2 variants. These findings have implications for vaccine protection against SARS-CoV-2 variants of concern.