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.

The impact of cross-reactive immunity on the emergence of SARS-CoV-2 variants

“…We also assumed a fixed level of cross-reactive immunity for all individuals who were previously infected by the related virus. In reality, immunity is heterogeneous between different previously infected hosts, and is likely to wane over time [53,54]. Waning immunity has been included previously in a range of epidemiological models [55,56], and is a target for future study in the modelling framework presented here.…”

The lymphatic system and COVID-19 vaccines

“…Because of these modifications, the COVID-19 mRNA vaccines are highly immunogenic, inducing strong serum neutralizing antibody responses in most individuals, whereas infection with SARS-CoV-2 produces more variable neutralizing antibody responses ( 19 , 20 ); in both cases, epitopes that overlap the ACE2-binding site in the RBD are targeted strongly by the generated antibodies. While neutralizing antibodies are a principal host defense mechanism against viral invasion, the mRNA COVID-19 vaccines also activate T cells, which play an important role in limiting disease severity and duration, as described below.…”

“…However, this issue seems to be more related to the pathogen than it is to the specific vaccines. A longitudinal study on SARS-CoV-2 reinfection indicates that, with natural infection, the mean time by which there is a 5% cumulative risk of reinfection was only approximately 140 days post-symptom onset, which is less than half of the mean time to a cumulative 5% risk of breakthrough infection following vaccination with Pfizer or Moderna mRNA vaccine (both required approximately 350 days post-vaccination to reach this point) ( 20 ). These results indicate that the immunity induced by SARS-CoV-2 natural infection begins to wane after several months post-infection and that the immunity from natural infection lasts for a much shorter length of time compared with the duration of vaccine-mediated immunity.…”

Lessons from a large-scale COVID-19 vaccine trial

“…Many participants were considered eligible to be unblinded and received a nonstudy COVID-19 vaccine before the end of the study (Figure 1B). Vaccine efficacy measures were stratified by age, sex at birth, race, ethnicity, BMI, comorbidities, OSHA risk categories, and participants' global regions of origin for the period of double-blinding (days after second vaccine dose) until receipt of nonstudy COVID-19 of vaccine efficacy can also be estimated by regression analysis of public health data sets (15); for example, in North Carolina, immune protection from mRNA-1273 and BNT162b2 vaccines lasted 7 months (11). As reported by Sobieszczyk and colleagues (1), a small number of infections with contemporaneous VOCs were observed in the vaccinated and placebo groups within the first 6 months after immunization; data collection was completed before the emergence of the Omicron strain.…”