Development of SARS-CoV-2 vaccines: challenges, risks, and the way forward

Abstract

The COVID-19 pandemic mandates the development of a safe and effective Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccine. This review analyzes the complexities, challenges, and other vital issues associated with the development of the SARS-CoV-2 vaccine. A brief review of the immune responses (innate, antibody, and T-cell) to SARS-CoV-2, including immune targets, correlates of protection, and duration of immunity is presented. Approaches to vaccine development including different vaccine platforms, critical attributes of novel vaccine candidates, the status of the ongoing clinical trials, and the ways to speed up vaccine development are also reviewed. Despite a historical average success rate of only 6%, and a usual gestation period of 10–12 years for the development of a new vaccine, the world is on the verge of developing COVID-19 vaccines in an extraordinary short time span.

Preliminary evidence on the safety profile of BNT162b2 ( Comirnaty ): new insights from data analysis in EudraVigilance and adverse reaction reports from an Italian health facility

“…The disease might become endemic; therefore, the primary intervention strategy for the control of SARS-CoV-2 transmission and infection is a safe and effective vaccine. 2,3 In Italy, since its first detection in February 2020, SARS-CoV-2 rapidly spread throughout the country, especially affecting the Lombardy Region and its capital Milan. To date, over 3 million Italians have been diagnosed with coronavirus disease 19 (COVID-19); the highest number of infected patients was reached on November 22nd 2020 with >800,000 confirmed cases.…”

Newcastle Disease Virus-Like Particles Displaying Prefusion-Stabilized SARS-CoV-2 Spikes Elicit Potent Neutralizing Responses

“…The majority of current SARS-CoV-2 vaccines and vaccine candidates in preclinical or clinical trials are based on the spike glycoprotein or the RBD. These use diverse vaccine delivery modalities, including mRNA, recombinant DNA, inactivated virus, and various viral vectors, and have been reported to elicit neutralizing antibodies, with primarily Th1-biased responses and up to 95% protection against symptomatic COVID-19 disease [3,5,[14][15][16][21][22][23][24][25][26][27]. To design second-generation SARS-CoV-2 vaccines, current efforts have focused on nanoparticle-based, viral-vector-based, or virus-derived replicon RNA-based vaccine candidates and virus-like particle (VLP) versions of immunogens.…”

Detection of IFNγ-Secreting CD4+ and CD8+ Memory T Cells in COVID-19 Convalescents after Stimulation of Peripheral Blood Mononuclear Cells with Live SARS-CoV-2

“…To date, over 190 million cases with more than 4 million fatalities have been registered worldwide, with many countries struggling in their third pandemic waves [ 1 ]. Specific SARS-CoV-2 vaccines have been developed with an unprecedented speed, and several safe and effective candidates have been released to the market less than a year since the virus emerged [ 2 , 3 ]. The human immune responses to natural SARS-CoV-2 infection and vaccination with various vaccines have been extensively studied and a huge amount of data accumulated, regarding the magnitude and the duration of antibody immunity, as well as T cell-based responses (reviewed in [ 4 , 5 ]).…”