The durability of natural infection and vaccine-induced immunity against future infection by SARS-CoV-2

Abstract

The durability of vaccine-mediated immunity to SARS-CoV-2, the durations to breakthrough infection, and the optimal timings of booster vaccination are crucial knowledge for pandemic response. Here, we applied comparative evolutionary analyses to estimate the durability of immunity and the likelihood of breakthrough infections over time following vaccination by BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford-AstraZeneca), and Ad26.COV2.S (Johnson & Johnson/Janssen). We evaluated anti-Spike (S) immunoglobulin G (IgG) antibody levels elicited by each vaccine relative to natural infection. We estimated typical trajectories of waning and corresponding infection probabilities, providing the distribution of times to breakthrough infection for each vaccine under endemic conditions. Peak antibody levels elicited by messenger RNA (mRNA) vaccines mRNA-1273 and BNT1262b2 exceeded that of natural infection and are expected to typically yield more durable protection against breakthrough infections (median 29.6 mo; 5 to 95% quantiles 10.9 mo to 7.9 y) than natural infection (median 21.5 mo; 5 to 95% quantiles 3.5 mo to 7.1 y). Relative to mRNA-1273 and BNT1262b2, viral vector vaccines ChAdOx1 and Ad26.COV2.S exhibit similar peak anti-S IgG antibody responses to that from natural infection and are projected to yield lower, shorter-term protection against breakthrough infection (median 22.4 mo and 5 to 95% quantiles 4.3 mo to 7.2 y; and median 20.5 mo and 5 to 95% quantiles 2.6 mo to 7.0 y; respectively). These results leverage the tools from evolutionary biology to provide a quantitative basis for otherwise unknown parameters that are fundamental to public health policy decision-making.

Keywords: COVID-19; SARS-CoV-2; antibody; immunity; vaccine.

Fig. 1.

Peak-normalized anti-S1 IgG antibody levels; probabilities of no breakthrough infection given antibody level; and probabilities of natural reinfection or breakthrough infection for Ad26.COV2.S, ChAdOx1, BNT162b2, and mRNA-1273 vaccinations against SARS-CoV-2 infection over 4,000 d postpeak response. (A) Peak-normalized anti-S1 IgG antibody levels for vaccination with Ad26.COV2.S (blue), vaccination with ChAdOx1 (green), natural infection (navy, dashed), vaccination with BNT162b2 (yellow, dashed), and vaccination with mRNA-1273 (orange, dashed) against SARS-CoV-2 infection over 4,000 d postpeak response and (Inset) over the first 400 d (just over 1 y) postpeak response. (B) Probability of no natural reinfection or no breakthrough infection for Ad26.COV2.S, ChAdOx1, BNT162b2, and mRNA-1273 vaccinations against SARS-CoV-2 infection over 4,000 d postpeak response and (Inset) over the first 400 d postpeak response. (C) Probabilities of natural reinfection or breakthrough infection for Ad26.COV2.S, ChAdOx1, BNT162b2, and mRNA-1273 vaccinations against SARS-CoV-2 infection over 4,000 d postpeak response and (Inset) over the first 1,000 d postpeak response.

Fig. 2.

Mean time to 5% cumulative risk of natural reinfection or breakthrough infection under endemic conditions for mRNA-1273, BNT162b2, ChAdOx1, and Ad26.COV2.S vaccinations against SARS-CoV-2.