Heterogeneity in vaccinal immunity to SARS-CoV-2 can be addressed by a personalized booster strategy

Abstract

The ongoing COVID-19 pandemic has placed an unprecedented burden on global health. Crucial for managing this burden, the existing SARS-CoV-2 vaccines have substantially reduced the risk of severe disease and death up to this point. The induction of neutralizing antibodies (nAbs) by these vaccines leads to protection against both infection and severe disease. However, pharmacokinetic (PK) waning and rapid viral evolution degrade neutralizing antibody binding titers, leading to a rapid loss of vaccinal protection against infection occurring on the order of months after vaccination. Additionally, inter-individual heterogeneity in the strength and durability of the vaccine-induced neutralizing response to SARS-CoV-2 can create a further public-health risk by placing a subset of the population at risk. Here we incorporate the heterogeneity in inter-individual response into a pharmacokinetic/ pharmacodynamic (PK/PD) model to project the degree of heterogeneity in immune protection. We extend our model-based approach to examine the impact of evolutionary immune evasion on vaccinal protection. Our findings suggest that viral evolution can be expected to impact the effectiveness of vaccinal protection against severe disease, particularly for individuals with a shorter duration of immune response. One possible solution to immune heterogeneity may be more frequent boosting for individuals with a weaker immune response. We demonstrate a model-based approach to targeted boosting that involves the use of the ECLIA RBD assay to identify individuals whose immune response is insufficient for protection against severe disease. Our work suggests that vaccinal protection against severe disease is not assured and provides a path forward to reducing the risk to immunologically vulnerable individuals.

Antibody escape, the risk of serotype formation, and rapid immune waning: modeling the implications of SARS-CoV-2 immune evasion

“…As we have explored in other analyses using agent-based models, the immunity landscape is more complex than this SIRS model can capture. This complexity arises due to heterogeneity in individual exposure to infection and vaccination, interindividual variability in antibody durability, and neutralizing antibody build-up over successive infections and vaccinations [42,57]. In particular, we surmise that the build-up of neutralizing potency over successive infections may cause the apparent cross-immunities between strains to not be fixed over time.…”

Vaccines alone cannot slow the evolution of SARS-CoV-2

“…NPIs complement vaccines in slowing viral evolution by limiting the transmission of novel vaccine-evading mutants (Figure 3). In the real world, vaccinal efficacy is degraded by two phenomena: the pharmacokinetic decay of neutralizing antibody titers and the rate of evolution of immune evasion by the virus (see [38] and Supplemental Text Section S8 in [39] for more details). We examined the hypothetical case of a vaccine whose efficacy was not degraded by immune-evading variants to identify the rate of vaccination required to prevent the generation of novel variants (Figure 4).…”

Shielding under endemic SARS-CoV-2 conditions is easier said than done: a model-based analysis

“…Vaccination is modeled similarly to infection, with neutralizing antibody titers increased by a fixed multiple upon vaccination. Vaccine antibodies are assumed to decay at the same rate as antibodies from natural infection, which is somewhat optimistic 88 . Each member of the simulated population is randomly designated as "vaccinated" or "unvaccinated" in a proportion consistent with the specified prevalence of vaccination in the population.…”