Long-term durability of immune responses to the BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex

Abstract

The lipid nanoparticle (LNP)-formulated mRNA vaccines BNT162b2 and mRNA-1273 are a widely adopted multi vaccination public health strategy to manage the COVID-19 pandemic. Clinical trial data has described the immunogenicity of the vaccine, albeit within a limited study time frame. Here, we use a within-host mathematical model for LNP-formulated mRNA vaccines, informed by available clinical trial data from 2020 to September 2021, to project a longer term understanding of immunity as a function of vaccine type, dosage amount, age, and sex. We estimate that two standard doses of either mRNA-1273 or BNT162b2, with dosage times separated by the company-mandated intervals, results in individuals losing more than 99% humoral immunity relative to peak immunity by 8 months following the second dose. We predict that within an 8 month period following dose two (corresponding to the original CDC time-frame for administration of a third dose), there exists a period of time longer than 1 month where an individual has lost more than 99% humoral immunity relative to peak immunity, regardless of which vaccine was administered. We further find that age has a strong influence in maintaining humoral immunity; by 8 months following dose two we predict that individuals aged 18–55 have a four-fold humoral advantage compared to aged 56–70 and 70+ individuals. We find that sex has little effect on the immune response and long-term IgG counts. Finally, we find that humoral immunity generated from two low doses of mRNA-1273 decays at a substantially slower rate relative to peak immunity gained compared to two standard doses of either mRNA-1273 or BNT162b2. Our predictions highlight the importance of the recommended third booster dose in order to maintain elevated levels of antibodies.

Monkeypox: A review of epidemiological modelling studies and how modelling has led to mechanistic insight

“…Serological features that inform us about immune responses can also be used by within-host modelling studies to reveal mechanistic insight into viral traits as well as vaccine dynamics. Interferon gamma (IFNg) is a cytokine known to play a pivotal role in host defence against pathogens [43,44], and is often used to model within-host inflammatory responses and infer cellular-mediated immunity [15,16]. Immunity from smallpox vaccination has been shown to elicit IFNg, cytotoxic T cell, and neutralizing protein responses in humans that can last over 20 years [45].…”

“…Modelling of in-host pathogen dynamics has proven critical towards furthering our understanding of HIV, HCV, HBV, HSV, influenza, and SARS-CoV-2 as well as aiding the development of vaccine therapies [8][9][10][11][12][14][15][16][118][119][120].…”

“…There have been historical efforts to quantify an immunological correlate of protection in humans against mpox [47], however, a robust correlate of protection against the 2022 strain is currently not known [38]. Serological studies can be leveraged by mathematical approaches to correlate humoral and cellular longitudinal responses with case severity, or vaccine efficacy, such as that done for SARS-CoV-2 [16]. It is also important to understand differences 22 in within-host dynamics amongst cohorts containing various comorbidities, notably high-risk individuals coinfected with syphilis or HIV [137].…”

“…Mathematical modelling has been used extensively to understand epidemics and inform intervention strategies [6,7]. Modelling of in-host pathogen dynamics has proven critical towards furthering our understanding of many pathogens such as HIV, HCV, HBV, HSV, influenza, pneumococcus, and SARS-CoV-2 as well as aiding the development of vaccine therapies [8][9][10][11][12][13][14][15][16]. This review focuses on the current epidemiological understanding of mpox from a modelling perspective and how modelling studies lead to mechanistic insight into viral fitness and transmission traits.…”

Determination of significant immunological timescales from mRNA-LNP-based vaccines in humans

“…In this paper we explore an in-host mathematical model for an LNP vaccine first considered by Korosec et al (2022) where computational mixed-effects modelling was used to identify model parameters from a variety of data sets. Their results demonstrated a diverse variability in the parameter estimates and consequently the model comparisons.…”