Vaccination promotes superior functional antibody breadth compared to natural infection with SARS-CoV-2

In a recent study posted on medrex sib*Preprint server, researchers can identify SARS-CoV-2 naturally occurring or messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) antibody (Ab) recognition in healthy and at-risk individuals after vaccination and the potency and breadth of effector function. .

Background

Emergence of Concern Variants (VOCs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Threatens COVID-19 Vaccines Effectiveness and serological immune responses. Immunity induced by vaccination and natural infection show some differences with respect to Ab responses. This may vary further among high-risk populations such as pregnant women. The breadth and magnitude of cross-reactive Ab effector functions has essential implications for the immune protection of diverse populations against further viral diversity.

About research

In the present study, researchers analyzed Ab Fc-mediated effector function and the magnitude and characteristics of Ab responses to SARS-CoV-2 VOC and endemic CoV in healthy and vulnerable individuals.

Sera received two doses of either mRNA-1273 (n=2) or BNT162b2 (n=85) vaccines and were exposed to SARS-CoV-2 during a period when the Wuhan-Hu-1 (ancestral) strain was dominant were obtained from vaccinated individuals (n =57), or had no previous exposure to SARS-CoV-2 [negative for SARS-CoV-2 nucleocapsid (N) protein, n=38]In addition, serum samples were obtained from 50 vaccinated pregnant women and 38 convalescent pregnant women (high-risk and immunologically vulnerable).

The diagnosis of COVID-19 was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) analysis in convalescent individuals. A UMAP (Uniform Variant Approximation and Projection) analysis was performed to assess differences and similarities in Ab profiles of seropositive individuals, and the team assessed correlations between ancestral strains and Ab isotypes with VOCs. In addition, the team investigated potential differences in FcγR tetrameric binding capacity and subclass between Abs for VOCs, as both mediate differences in Ab effector function.

Immunoglobulin A (IgA), IgG, and IgM bread scores and potency curves were obtained for VOCs tested across the SARS-CoV-2 spike (S) protein or across the S protein receptor binding domain (RBD) . For all participants, Ab-dependent cytotoxicity (ADCC), Ab-dependent complement deposition (ADCD), and phagocytic activity were assessed across S or S RBDs. antigen against the VOCs tested.

Furthermore, the team investigated whether Ab Fc effector function is induced by Middle East respiratory syndrome (MERS) CoV, SARS-CoV-1, beta(β)-CoV HKU1 and OC4, alpha(α)-CoV 229E and NL63. I investigated. For antigen and Fc receptor expression, SARS-CoV-2 antigen was transiently expressed in HeK293 or Expi293 cells and antigen-specific Abs were characterized using Fc array assays. Antigen-specific Abs specific for human Ig isotypes and subclasses were assessed, and phagocytosis was assessed based on flow cytometry (FC) analysis and mean fluorescence intensity (MFI) scores.

result

Similar binding and functional breadth were observed between healthy individuals and immunologically vulnerable pregnant women. Ab responses were strongly correlated with IgG rather than IgA, S RBD rather than S whole, and vaccinated rather than recoverers. However, greater Ab function against OC43 was observed during recovery, indicating a dichotomous recognition between distant and short-range human CoV (hCoV) associated with COVID-19 history.

The breadth of IgM Abs was greater in convalescent patients, the breadth of IgG Abs was greater in vaccinated subjects, and the breadth of IgA Abs was comparable between the two groups. A strong inter-VOC correlation was observed for IgG. IgM Ab breadths were greater in convalescent patients than in mRNA vaccinated subjects, IgA titers were similar between the two groups, and IgG Ab breadths were significantly greater among vaccinated subjects, more than S overall. There was a more pronounced difference in S RBD.

Titers of IgG subclasses (especially IgG1 and 3) were stronger and more widespread across VOCs in SARS-CoV-2-uninfected individuals than in seropositive individuals. Differences in width between subclasses between vaccinated and recoverers were greater for S RBD than for full-length S. S RBD is larger than total length S.

Functional Ab responses, with the exception of complement deposition to the ancestral strain full-length S, were comparable or superior among vaccinated against the ancestral strain and SARS-CoV-2 VOC compared to recoverers. Functional Ab responses to S RBD differ most significantly among vaccinated individuals in complement deposition and ADCC to beta- and gamma-VOC RBDs.

The breadth scores obtained for all effector functions showed significantly improved breadth of cross-reactive functional Ab responses among vaccinated persons over recoverers to S and S RBDs overall. Potent effector function targeting SARS-CoV-1 was noted in full-length S and subunit S1 among vaccinated persons, whereas among convalescent individuals, cross-reactivity to the target was noted. A functional Ab response was lacking.

In contrast, strong Ab activity was observed against the full-length S and subunit S2 of OC43 in recovery phase. Greater phagocytosis was observed in her HKU1 and OC43 among convalescent patients and vaccinated persons, respectively. However, neither group phagocytosed MERS S and αCoV NL63 and 229E.

Conclusion

Overall, this study showed that vaccination induced functional Ab breadth responses superior to natural SARS-CoV-2 infection. Both vaccination and natural infection induce Abs with a wider range of conserved effector functions than neutralizing functions.

*Important Notices

medRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .