Understanding “Hybrid Immunity”: Comparison and Predictors of Humoral Immune Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19) Vaccines

Abstract

Background Comparing humoral responses in SARS-CoV-2 vaccinees, those with SARS-CoV-2 infection, or combinations of vaccine/infection (‘hybrid immunity’), may clarify predictors of vaccine immunogenicity. Methods We studied 2660 U.S. Military Health System beneficiaries with a history of SARS-CoV-2 infection-alone (n = 705), vaccination-alone (n = 932), vaccine-after-infection (n = 869), and vaccine-breakthrough-infection (n = 154). Peak anti-spike-IgG responses through 183 days were compared, with adjustment for vaccine product, demography, and comorbidities. We excluded those with evidence of clinical or sub-clinical SARS-CoV-2 reinfection from all groups. Results Multivariable regression results indicated vaccine-after-infection anti-spike-IgG responses were higher than infection-alone (p < 0.01), regardless of prior infection severity. An increased time between infection and vaccination was associated with a greater post-vaccination IgG response (p < 0.01). Vaccination-alone elicited a greater IgG response, but more rapid waning of IgG (p < 0.01), compared to infection-alone (p < 0.01). BNT162b2 and mRNA-1273 vaccine-receipt was associated with greater IgG responses compared to JNJ-78436735 (p < 0.01), regardless of infection history. Those with vaccine-after-infection or vaccine-breakthrough-infection had a more durable anti-spike-IgG response compared to infection-alone (p < 0.01). Conclusions Vaccine-receipt elicited higher anti-spike-IgG responses than infection-alone, although IgG levels waned faster in those vaccinated (compared to infection-alone). Vaccine-after-infection elicits a greater humoral response compared to vaccine or infection alone; and the timing, but not disease severity, of prior infection predicted these post-vaccination IgG responses. While differences between groups were small in magnitude, these results offer insights into vaccine immunogenicity variations that may help inform vaccination timing strategies.

Post-vaccination Omicron infections induce broader immunity across antigenic space than prototype mRNA COVID-19 booster vaccination or primary infection

“…To measure the antigenic relationships among variants using well-characterized primary infection antisera, we used sera from SARS-CoV-2 infected participants from the Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study ( Table S1 ) (Epsi et al, 2022). We identified n=47 serum samples collected 8 to 51 days post symptom onset (mean=28 days) from individuals with natural primary infections with 21 distinct variants (all prior to vaccination).…”

Cumulative incidence of SARS-CoV-2 infection in the general population of the Valencian Community (Spain) after the surge of the Omicron BA.1 variant

“…The copyright holder for this preprint this version posted July 19, 2022. ; https://doi.org/10.1101/2022.07. 19.22277747 doi: medRxiv preprint 12 VAC-ex individuals, whereas a moderate inverse correlation (Rho, -0 52; 95% CI, -0 59 to -0 45; P<0 001) was observed in VAC-n (Figure 2). Interestingly, in VACex participants with a recorded positive AIDT result [n=220] (Figure 3), the time elapsed since documentation of SARS-CoV-2 infection correlated weakly (inversely) with anti-RBD antibody levels (Rho, -0 30; 95% CI -42 to -0 17; P<0 001).…”

“…The copyright holder for this preprint this version posted July 19, 2022. ; https://doi.org/10.1101/2022.07. 19.22277747 doi: medRxiv preprint…”

“…The copyright holder for this preprint this version posted July 19, 2022. ; https://doi.org/10.1101/2022.07. 19.22277747 doi: medRxiv preprint unvaccinated/experienced (UNVAC-ex, unvaccinated population with history or serological evidence of prior SARS-CoV-2 infection), and unvaccinated/naïve (UNVAC-n, unvaccinated population with no history or serological evidence of prior SARS-CoV-2 infection). AIDTs included rapid antigen-detection assays targeting the N protein or commercially-available RT-PCRs.…”

“…The copyright holder for this preprint this version posted July 19, 2022. ; https://doi.org/10.1101/2022.07. 19.22277747 doi: medRxiv preprint (sub)variants by an S-pseudotyped neutralization assay and for enumeration of SARS-CoV-2-S specific-IFNγ-producing CD4 + and CD8 + T cells by Intracellular Cytokine Staining assay was performed in a subset of participants (n=100 and 137, respectively).…”