What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2

Abstract

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 1 million deaths in the first 6 months of the pandemic and huge economic and social upheaval internationally. An efficacious vaccine is essential to prevent further morbidity and mortality. Although some countries might deploy COVID-19 vaccines on the strength of safety and immunogenicity data alone, the goal of vaccine development is to gain direct evidence of vaccine efficacy in protecting humans against SARS-CoV-2 infection and COVID-19 so that manufacture of efficacious vaccines can be selectively upscaled. A candidate vaccine against SARS-CoV-2 might act against infection, disease, or transmission, and a vaccine capable of reducing any of these elements could contribute to disease control. However, the most important efficacy endpoint, protection against severe disease and death, is difficult to assess in phase 3 clinical trials. In this Review, we explore the challenges in assessing the efficacy of candidate SARS-CoV-2 vaccines, discuss the caveats needed to interpret reported efficacy endpoints, and provide insight into answering the seemingly simple question, “Does this COVID-19 vaccine work?”

First report demonstrating the safety and immunogenicity of the SARS-COV-2 BNT162b1 mRNA vaccine in younger and older Chinese adults: a randomized, placebo-controlled, observer-blind Phase I study

“…All laboratory abnormalities were self-limited and resolved in a short period of time without clinical manifestations (Extended Data Figure 4). These data are in line with the results seen in EudraCT 2020-001038-36 study, and other RNA vaccine trials that have found CRP levels 15,16 and lymphocyte counts 17 to act as pharmacodynamic markers for the mode-of-action of these vaccines.…”

“…Evaluating the tolerability, safety and immunogenicity of SARS-COV-2 prophylactic RNA vaccines in Asian children and adolescent populations is further warranted. Secondly, although the serum-neutralizing responses elicited by the BNT162b1 vaccine candidate were compared with that in human convalescent serum panels, the level of serological immunity needed to protect against COVID- 19 has not yet been determined 15 . In addition, the human convalescent serum panels that have been used in different trials are not standardized among laboratories, and each have a different distribution of patient characteristics and timepoints of collection, which imposes challenging in immunogenicity comparisons across studies and different vaccines.…”

The role of weather conditions in COVID-19 transmission: A study of a global panel of 1236 regions

“…Theoretically, A candidate vaccine against SARS-CoV-2 might act against infection, disease, or transmission, and a vaccine capable of reducing any of these elements could contribute to disease control. As Hodgson et al. (2020) , Peiris and Leung (2020) mention, the transmission would not be terminated if effective vaccines are available.…”

High Rates of COVID-19 Vaccine Hesitancy and Its Association with Conspiracy Beliefs: A Study in Jordan and Kuwait among Other Arab Countries

“…An essential tool for controlling the ongoing COVID-19 pandemic is the availability of efficacious vaccine(s), which can help in reducing transmission, hospital admissions and the demand on intensive care [ 16 ]. Governments supported the pharmaceutical industry and academic community to direct huge efforts towards the development of safe and effective vaccines, among therapeutics and rapid diagnostics [ 17 , 18 ].…”