COVID-19 Vaccines: A Race Against Time in the Middle of Death and Devastation!

Abstract

The coronavirus disease 2019 (COVID-19) has turned into a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in Research & Development by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks, and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are "rate-limiting" and "time-consuming", many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human "challenge experiments" to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine, and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying "Quick fix" and "short cuts" can lead to errors with disastrous consequences.

Keywords: ADE, Antibody-Dependent Enhancement; CEPI, Coalition for Epidemic Preparedness Innovations; COVID-19; COVID-19, Coronavirus Disease 2019; MERS-CoV, Middle East Respiratory Syndrome Coronavirus; MHC, Major Histocompatibility Complex; SARS-CoV-2; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; WHO, World Health Organization; coronavirus; platform technology clinical trials; vaccine.

Figure 1

Schematic drawing of 8 platform strategies used for the development of COVID-19 vaccines, and the pathway each one follows to induce T cell and B cell immune response. The strategies include live-attenuated vaccine (LA), inactivated vaccine (IA), DNA vaccine (DNA), RNA vaccine (RNA), viral vector replicating vaccine (VVR), viral vector nonreplicating (VVNR), virus-like particles (VLP), and subunit vaccine (Subunit). CV, coronavirus; APC, antigen processing cell.

Figure 2

Schematic drawing depicting FCγ receptor (FCγR)–mediated antibody-mediated enhancement. This response is mediated by the type of nonneutralizing antibodies mounted against infection or vaccination. The immune response to such vaccines is subverted, leading to exacerbated illness. The Fc-region of the antibody binds to FCγR on the immune cells, which subverts the immune response by reducing T_H1 cytokines (IL-2, TNF-a, and IFN-γ) and skews T_H2 cytokines (IL-10, IL-6, PGE-2, and INF-ά) and inhibits STAT pathway leading to increased viral replication. STAT-A, signal transducer and activator of transcription protein-A; IRF, interferon regulatory factor, INOS, inducible nitric oxide synthase.

Figure 3

Schematic drawing showing steps in vaccine development. The vaccine development follows a unique stepwise pattern and is broadly divided into Exploratory, Preclinical, Clinical, and Postmarketing stages. The clinical stage is divided into 3 phases, namely phases I, II, and III. There are 2 regulatory permissions needed namely “Clinical Trial Authorization” before the clinical stage to allow “First-in-human” testing and marketing of the vaccine after successful clinical trials.