Correlates of Vaccine-Induced Protection against SARS-CoV-2

Abstract

We are in the midst of a pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). SARS-CoV-2 has caused more than two million deaths after one year of the pandemic. The world is experiencing a deep economic recession. Safe and effective vaccines are needed to prevent further morbidity and mortality. Vaccine candidates against COVID-19 have been developed at an unprecedented speed, with more than 200 vaccine candidates currently under investigation. Among those, 20 candidates have entered the clinical Phase 3 to evaluate efficacy, and three have been approved by the European Medicines Agency. The aim of immunization is to act against infection, disease and/or transmission. However, the measurement of vaccine efficacy is challenging, as efficacy trials need to include large cohorts with verum and placebo cohorts. In the future, this will be even more challenging as further vaccine candidates will receive approval, an increasing number of humans will receive vaccinations and incidence might decrease. To evaluate novel and second-generation vaccine candidates, randomized placebo-controlled trials might not be appropriate anymore. Correlates of protection (CoP) could be an important tool to evaluate novel vaccine candidates, but vaccine-induced CoP have not been clearly defined for SARS-CoV-2 vaccines. In this review, we report on immunogenicity against natural SARS-CoV-2 infection, vaccine-induced immune responses and discuss immunological markers that can be linked to protection. By discussing the immunogenicity and efficacy of forerunner vaccines, we aim to give a comprehensive overview of possible efficacy measures and CoP.

Comparative immunogenicity of mRNA and inactivated vaccines against COVID-19

“…Neutralising antibody titres have been proposed as a correlate of protection for SARS-CoV-2 vaccines. 3 , 4 , 5 The difference in concentrations of neutralising antibodies identified in our study could translate into substantial differences in vaccine effectiveness. Our study did not include data on other potential correlates of protection such as T cells or antibody-dependent cellular cytotoxicity antibody.…”

Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19

“…Adding to the complexity of this situation is the fact that no correlate of protection has been defined for any highly pathogenic coronavirus 8 , 9 and the concern that such correlates might differ among vaccines 10 . Nonetheless, a protective role for both humoral and cell-mediated immunity against coronaviruses has been suggested 11 , 12 .…”

Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

“…The immune correlates of protection against infection and disease caused by SARS-CoV-2 are imperfectly understood (reviewed by 8 , 9 ). Classically, neutralization by antibody, measured by reduction in plaque or infectious foci by authentic virus in vitro is considered a major component of protection.…”