Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

Abstract

Vaccines represent one of the major advances of modern medicine. Despite the many successes of vaccination, continuous efforts to design new vaccines are needed to fight “old” pandemics, such as tuberculosis and malaria, as well as emerging pathogens, such as Zika virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccination aims at reaching sterilizing immunity, however assessing vaccine efficacy is still challenging and underscores the need for a better understanding of immune protective responses. Identifying reliable predictive markers of immunogenicity can help to select and develop promising vaccine candidates during early preclinical studies and can lead to improved, personalized, vaccination strategies. A systems biology approach is increasingly being adopted to address these major challenges using multiple high-dimensional technologies combined with in silico models. Although the goal is to develop predictive models of vaccine efficacy in humans, applying this approach to animal models empowers basic and translational vaccine research. In this review, we provide an overview of vaccine immune signatures in preclinical models, as well as in target human populations. We also discuss high-throughput technologies used to probe vaccine-induced responses, along with data analysis and computational methodologies applied to the predictive modeling of vaccine efficacy.

Reactogenicity Correlates Only Weakly with Humoral Immunogenicity after COVID-19 Vaccination with BNT162b2 mRNA (Comirnaty®)

“…This notion is strongly supported by our present findings that AEs correlated only weakly with the SARS-CoV-2 antibody levels after a COVID-19 vaccination with BNT162b2 mRNA and that the intake of anti-inflammatory drugs did not affect the anti-SARS-CoV-2 antibody response. Current and future systems' immunology approaches aim to dissect the signals that account for AEs and that are required for immunogenicity and clinical vaccine efficacy [29,30].…”

Differential Dynamics of SARS-CoV-2 Binding and Functional Antibodies upon BNT162b2 Vaccine: A 6-Month Follow-Up

“…Although immune responses to infections are multifaceted, antibody based markers are often used as correlate of protection [6]. The advantage of binding antibodies markers…”

Anti-SARS-CoV-2 antibody levels and kinetics of vaccine response: potential role for unresolved inflammation following recovery from SARS-CoV-2 infection

“…Similar to the clinical response to the SARS-CoV-2, the immune response after vaccine administration appears to be characterized by high inter-individual variation 10 . The identification of markers of immunogenicity can help to improve vaccine development and personalized vaccination strategies 11 – 13 . Host-specific factors associated with the efficacy of anti-SARS-CoV-2 vaccines are not yet clearly outlined, although they may include all factors affecting immune system functionality, such as, beyond genetics, age, sex, psychosocial factors, lifestyles, microbiota, drugs, clinical history, and other previous vaccinations, as well as a basal inflammatory state 14 , as confirmed by recent studies 15 – 18 .…”