Post-vaccination SARS-CoV-2 antibody kinetics and protection duration against Omicron in elderly population.
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ABSTRACT:
SUBMITTER: Dimeglio C
PROVIDER: S-EPMC9439860 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
Publications
Post-vaccination SARS-CoV-2 antibody kinetics and protection duration against Omicron in elderly population.
Dimeglio Chloé C Trémeaux Pauline P Herin Fabrice F Da-Silva Isabelle I Porcheron Marion M Martin-Blondel Guillaume G Gernigon Caroline C Chapuy-Regaud Sabine S Villars Hélène H Izopet Jacques J
The Journal of infection 20220903 6
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Project description:Antibodies represent a primary mediator of protection against respiratory viruses such as SARS-CoV-2. Serum neutralizing antibodies (NAbs) are often considered a primary correlate of protection. However, detailed antibody profiles including characterization of antibody functions in different anatomic compartments are not well understood. Here we show that antibody correlates of protection against SARS-CoV-2 challenge are different in systemic versus mucosal compartments in rhesus macaques. In serum, neutralizing antibodies were the strongest correlate of protection and were linked to Spike-specific binding antibodies and other extra-neutralizing antibody functions that create a larger protective network. In contrast, in bronchiolar lavage (BAL), antibody-dependent cellular phagocytosis (ADCP) proved the strongest correlate of protection rather than NAbs. Within BAL, ADCP was linked to mucosal Spike-specific IgG, IgA/secretory IgA, and Fcγ-receptor binding antibodies. Our results support a model in which antibodies with different functions mediate protection at different anatomic sites. The correlation of ADCP and other Fc functional antibody responses with protection in BAL suggests that these antibody responses may be critical for protection against SARS-CoV-2 Omicron challenge in mucosa.
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Project description:BackgroundThe quantitative level and kinetics of neutralizing antibodies (NAbs) in individuals with Omicron breakthrough infections may differ from those of vaccinated individuals without infection. Therefore, we aimed to evaluate the difference in NAb levels to distinguish the breakthrough cases from the post-immunized population to identify early infected person in an outbreak epidemic when nasal and/or pharyngeal swab nucleic acid real-time PCR results were negative.MethodsWe collected 1077 serum samples from 877 individuals, including 189 with Omicron BA.2 breakthrough infection and 688 post-immunized participants. NAb titers were detected using the surrogate virus neutralization test, and were log(2)-transformed to normalize prior to analysis using Student's unpaired t-tests. Geometric mean titers (GMT) were calculated with 95% confidence intervals (CI). Linear regression models were used to identify factors associated with NAb levels. We further conducted ROC curve analysis to evaluate the NAbs' ability to identify breakthrough infected individuals in the vaccinated population.ResultsThe breakthrough infection group had a consistently higher NAb levels than the post-immunized group according to time since the last vaccination. NAb titers in the breakthrough infection group were 6.4-fold higher than those in the post-immunized group (GMT: 40.72 AU/mL and 6.38 AU/mL, respectively; p<0.0001). In the breakthrough infection group, the NAbs in the convalescent phase were 10.9-fold higher than in the acute phase (GMT: 200.48 AU/mL and 18.46 AU/mL, respectively; p<0.0001). In addition, the time since infection, booster vaccination, and the time since last vaccination were associated with log(2)-transformed NAb levels in the breakthrough infection group. ROC curve analysis showed that ROC area was largest (0.728) when the cut-off value of log(2)-transformed NAb was 6, which indicated that NAb levels could identify breakthrough infected individuals in the vaccinated population.ConclusionOur study demonstrates that the NAb titers of Omicron BA.2 variant breakthrough cases are higher than in the post-immunized group. The difference in NAb levels could be used to identify cases of breakthrough infection from the post-immunized population in an outbreak epidemic.
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