How does hybrid immunity shape the humoral immune response to SARS-CoV-2?

In a recent study published on the medRxiv * prepress server, researchers illustrated that hybrid immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) expands the effective humoral signatures of SARS-CoV-2 vaccinations. .

Study: Hybrid immunity expands the functional humoral footprint of both mRNA vaccines and vector-based SARS-CoV-2 vaccines. Image credit: vitstudio / Shutterstock

Fund

The SARS-CoV-2 pandemic brought about a breakthrough in vaccine development, leading to the detection and approval of a number of global vaccine platforms that have proven to be very promising to contain the pandemic. However, declining immunity and the emergence of SARS-CoV-2 (VOC) concern variants associated with an increase in innovative vaccine infections have begun to emphasize opportunities to improve vaccine platforms and administration.

The reduced risk of infections and advanced diseases in those infected and vaccinated by SARS-CoV-2, also known as hybrid immunity, has been underlined by the effectiveness of the CoV 2019 vaccine (COVID-19) in the world real. Hybrid immunity suggests the possibility of a more robust or unique immunity prepared for infection and could provide better protection against COVID-19. It is possible to characterize the immunological correlates of COVID-19 protection to target rational booster vaccination and the development of new generation vaccines against newly developed viral VOCs by identifying platform-specific immune programming variations and how they can be modified by hybrid immunity.

About the study

The current study aimed to determine whether hybrid immunity could influence functional humoral immune response to SARS-CoV-2 apart from enhanced immunity of T cells and neutralizing antibodies after vaccination with Modern mRNA1273 and Pfizer / BNT162b2 messenger ribonucleic acid (mRNA) based on ChadOx1. / AZ1222 and Ad26.COV2.S vector-based COVID-19 vaccines.

The team examined serum samples from individuals with and without a history of COVID-19 with a complete vaccination status using any of the four existing SARS-CoV-2 vaccines. Subjects received two doses of BNT162b2 mRNA (Pfizer) or mRNA-1273 (Modern) vaccines, one dose of the Ad26.COV2.S (Janssen) vector vaccine of human adenovirus type 26 (Ad26), or two doses of the vaccine vectorized by ChAdOx. vaccine AZ1222 (AstraZeneca). Blood samples were collected at the maximum immunogenicity time marks specified for each vaccine for averages of eight, eight, 34, and seven days after the final dose of the Pfizer, Moderna, Janssen, and AstraZeneca vaccines, respectively.

Results and conclusions

The results of the study indicated that each vaccine against COVID-19 examined showed different functional humoral immune characteristics in the context of a hybrid or naive immunity. The different inflammatory signals elicited at the time of vaccination were probably related to the peculiar antibody functional profile produced by each vaccine. The different functional antibody profile directs class-specific switching recombination and glycosylation patterns of crystallizable fragments (Fc) in the auxiliary T and B cell reactions. Collectively they model the general characteristics of binding of the Fc receptor (FcR) and effector of polyclonal colonies of antibodies caused by the vaccine.

The authors found that hybrid immunity also influences antibody effector activities, with drastic improvements in antibody reaction and FcR adhesion after a single dose of vector vaccine and a tendency for further expansion of antibodies. concentrations and function after the second dose of AZD1222. IgA and IgG titers for mRNA vaccines specific to subunit 2 (S2) of the SARS-CoV-2 (S) subunit increased significantly as a result of hybrid immunity, indicating a preferential increase of immunity to the conserved region of the S antigen, with only patterns in the IgG1 titer and increased with the second dose of mRNA. In contrast, DNAP increased markedly after the initial and second doses of mRNA vaccinations in those with hybrid immunity.

In addition, after considering demography, S2-specific FcR adhesion was preferentially improved in mRNA vaccines that had hybrid immunity. In fact, those vaccinated with AZD1222 also showed this trait. The structural sustainability of the S2 domain and the cross-reactivity and neutralizing capacity of S2 antibodies can reduce the impact of sequence-altering mutations. As a result, they could increase the effectiveness of vaccines against seasonal common cold VOCs and emerging VOCs.

Overall, the study data emphasize the immunodominant impact of the S1 domain in the context of SARS-CoV-2 natural immunity. The SARS-CoV-2 S1 domain was substantially variable in viral evolution. The present research further points to the importance of natural infection in overcoming S1 immunodominance and triggering immunity in the S2 areas of the SARS-CoV-2 S2 domain, which are more conserved among VOCs.

* Important news

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guided by clinical practice or health-related behavior, or treated as established information.

Magazine reference:

  • Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines; Paulina Kaplonek, Yixiang Deng, Jessica Shih-Lu Lee, Heather Zar, Dace Zavadska, Marina Johnson, Douglas A Lauffenburger, David Goldblatt, Galit Alter. medRxiv preprint 2022, DOI:

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