| Abstract |
Hybrid immunity (vaccination + natural infection) to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters to evaluate hybrid immunity induction. The mRNA vaccine, BNT162b2, was dosed to induce binding antibody titers against ancestral spike, but inefficient serum virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs). Vaccination reduced morbidity and controlled lung virus titers for ancestral virus and Alpha but allowed breakthrough infections in Beta, Delta and Mu-challenged hamsters. Vaccination primed for T cell responses that were boosted by infection. Infection back-boosted neutralizing antibody responses against ancestral virus and VoCs. Hybrid immunity resulted in more cross-reactive sera, reflected by smaller antigenic cartography distances. Transcriptomics post-infection reflects both vaccination status and disease course and suggests a role for interstitial macrophages in vaccine-mediated protection. Therefore, protection by vaccination, even in the absence of high titers of neutralizing antibodies in the serum, correlates with recall of broadly reactive B- and T-cell responses. |
| Authors |
Juan García-Bernalt Diego  , Gagandeep Singh , Sonia Jangra , Kim Handrejk , Manon Laporte , Lauren A. Chang , Sara S. El Zahed , Lars Pache , Max W. Chang  , Prajakta Warang , Sadaf Aslam , Ignacio Mena , Brett T. Webb , Christopher Benner , Adolfo García‐Sastre , Michael Schotsaert
|
| Journal Info |
Public Library of Science | PLOS Pathogens , vol: 20
, iss: 1
, pages: e1011805 - e1011805
|
| Publication Date |
1/10/2024 |
| ISSN |
1553-7366 |
Type |
article |
| Open Access |
gold
|
| DOI |
https://doi.org/10.1371/journal.ppat.1011805 |
| Keywords |
Immunity (Score: 0.526119)
|
