Longevity of hybrid immunity against SARS-CoV-2 in adults vaccinated with an adenovirus-based COVID-19 vaccine

Abstract

Background: Hybrid immunity provides better protection against COVID-19 than vaccination or prior natural infection alone. It induces high magnitude and broadly cross-reactive neutralising anti-Spike IgG antibodies. However, it is not clear how long these potent antibodies last, especially in the context of adenovirus-based COVID-19 vaccines.

Methods: We conducted a longitudinal cohort study and enrolled 20 adults who had received an adenovirus-based COVID-19 vaccine before a laboratory-confirmed SARS-CoV-2 infection. We followed up the study participants for 390 days post the initial breakthrough infection. We assessed the longevity and cross-reactive breadth of serum antibodies against SARS-CoV-2 variants of concern (VOCs), including Omicron.

Results: The binding anti-Spike IgG antibodies remained within the reported putative levels for at least 360 days and were cross-neutralising against Beta, Gamma, Delta, and Omicron. During the follow up period, a median of one SARS-CoV-2 re-infection event was observed across the cohort, but none resulted in severe COVID-19. Moreover, the re-exposure events were associated with augmented anti-Spike and anti-RBD IgG antibody titres.

Conclusions: This study confirms that hybrid immunity provides durable broadly cross-reactive antibody immunity against SARS-CoV-2 variants of concern for at least a year (360 days), and that it is further augment by SARS-CoV-2 re-exposure.

Keywords: Breakthrough infection; Hybrid immunity; Longevity; SARS-CoV-2.

Fig. 1

Serum IgG antibody kinetics. Box plots showing (a) anti-RBD IgG and (b) anti-Spike IgG antibody concentrations for n=20 individuals, post initial breakthrough infection. The dotted line represents reported putative protective anti-Spike IgG levels. The horizontal bars represent the median and interquartile range (IQR). Data was log 10 transformed and statistics were calculated using Wilcoxon rank sum test and p value adjusted for multiple comparisons using the Bonferroni multiple comparisons test. A p<0.05 was regarded as statistically significant. All visits were compared to day 60, and only p values <0.1 are shown on the graph. WT, Wild-type; RBD, Receptor Binding Domain; WHO BAU, World Health Organization Binding Antibody Units

Fig. 2

Anti-SARS-CoV-2 variants serum IgG antibody kinetics. Box plots showing (a) anti-Alpha Spike IgG, (b) anti-Beta Spike IgG, (c) anti-Gamma Spike IgG, (d) anti-Delta Spike IgG, and (e) anti-Omicron (B.1.1.529) Spike IgG antibody concentrations for n=20 individuals, post initial breakthrough infection. The horizontal bars represent the median and interquartile range (IQR). Data was log 10 transformed. MSD AU, Meso Scale Discovery Arbitrary Units

Fig. 3

SARS-CoV-2 IgG Nucleocapsid antibody kinetics post initial breakthrough infection. a Anti-nucleocapsid concentrations overtime in serum samples after the first breakthrough infection (n=20). Data was log transformed. b Number of reinfections determined by a 2-fold increase in anti-Nucleocapsid IgG antibodies (n=20). c Corresponding increase in anti-Spike IgG antibodies in individuals with 2-fold increase in anti-Nucleocapsid IgG antibodies (n=14). Data was log 10 transformed and statistics were calculated using Wilcoxon signed rank test. WHO BAU, World Health Organization Binding Antibody Units

Fig. 4

Antibody neutralisation capacity post SARS-CoV-2 breakthrough infection overtime. Box plots showing magnitude of neutralising antibodies against (a) anti-RBD ACE2 inhibiting antibodies and (b) anti-Spike ACE2 inhibiting antibodies. The horizontal bars represent the median and interquartile range (IQR). Statistics were calculated using Wilcoxon rank sum test and p value adjusted for multiple comparisons using Bonferroni multiple comparisons test. A p<0.05 was regarded as statistically significant. Radar charts in (c-e) represent median ACE2 inhibitory percentages against VOCs (Wild type, Alpha, Beta, Delta, Gamma, and Omicron) calculated at 90 days, 240 days, and 360 days post initial SARS-CoV-2 breakthrough infection