Hybrid immunity and vaccine breakthrough lead to robust humoral response and antibodies that effectively neutralize SARS-CoV-2 variants

• Published in: The Journal of immunology (1950) 2022-05, Vol.208 (1_Supplement), p.65-65.12
• Main Authors: Bates, Timothy A, McBride, Savannah K, Leier, Hans C, Lyski, Zoe L, Messer, William B, Curlin, Marcel E, Tafesse, Fikadu G.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.208.Supp.65.12

Current COVID-19 vaccines significantly reduce overall morbidity and mortality and are vitally important to halting the pandemic; individuals who previously recovered from COVID-19 display enhanced immune responses after vaccination (hybrid immunity) compared to their naïve-vaccinated peers. However, the effects of vaccine breakthrough infections on humoral immune response remain to be determined. Here, we measure neutralizing antibody responses from 104 vaccinated individuals including those with breakthrough infections, hybrid immunity, and no infection history. We find that human immune sera collected after either a breakthrough infection or a vaccination post-natural infection will both broadly neutralize SARS-CoV-2 variants to a similar degree. While age negatively correlates with antibody response after vaccination alone, no such association was found in breakthrough or hybrid immune groups. Together, our data suggest that the additional antigen exposure from natural infection substantially boosts the quantity, quality, and breadth of humoral immune response regardless of whether it occurs before or after vaccination. Supported by grants from the M.J. Murdock Charitable Trust, OHSU Innovative IDEA grant (1018784),  NIH (R01AI145835, T32HL083808), and an unrestricted grant from the OHSU Foundation.