Insights into COVID-19 Vaccine Development Based on Immunogenic Structural Proteins of SARS-CoV-2, Host Immune Responses, and Herd Immunity

Abstract

The first quarter of the 21st century has remarkably been characterized by a multitude of challenges confronting human society as a whole in terms of several outbreaks of infectious viral diseases, such as the 2003 severe acute respiratory syndrome (SARS), China; the 2009 influenza H1N1, Mexico; the 2012 Middle East respiratory syndrome (MERS), Saudi Arabia; and the ongoing coronavirus disease 19 (COVID-19), China. COVID-19, caused by SARS-CoV-2, reportedly broke out in December 2019, Wuhan, the capital of China’s Hubei province, and continues unabated, leading to considerable devastation and death worldwide. The most common target organ of SARS-CoV-2 is the lungs, especially the bronchial and alveolar epithelial cells, culminating in acute respiratory distress syndrome (ARDS) in severe patients. Nevertheless, other tissues and organs are also known to be critically affected following infection, thereby complicating the overall aetiology and prognosis. Excluding H1N1, the SARS-CoV (also referred as SARS-CoV-1), MERS, and SARS-CoV-2 are collectively referred to as coronaviruses, and taxonomically placed under the realm Riboviria, order Nidovirales, suborder Cornidovirineae, family Coronaviridae, subfamily Orthocoronavirinae, genus Betacoronavirus, and subgenus Sarbecovirus. As of 23 September 2021, the ongoing SARS-CoV-2 pandemic has globally resulted in around 229 million and 4.7 million reported infections and deaths, respectively, apart from causing huge psychosomatic debilitation, academic loss, and deep economic recession. Such an unprecedented pandemic has compelled researchers, especially epidemiologists and immunologists, to search for SARS-CoV-2-associated potential immunogenic molecules to develop a vaccine as an immediate prophylactic measure. Amongst multiple structural and non-structural proteins, the homotrimeric spike (S) glycoprotein has been empirically found as the most suitable candidate for vaccine development owing to its immense immunogenic potential, which makes it capable of eliciting both humoral and cell-mediated immune responses. As a consequence, it has become possible to design appropriate, safe, and effective vaccines, apart from related therapeutic agents, to reduce both morbidity and mortality. As of 23 September 2021, four vaccines, namely, Comirnaty, COVID-19 vaccine Janssen, Spikevax, and Vaxzevria, have received the European Medicines Agency’s (EMA) approval, and around thirty are under the phase three clinical trial with emergency authorization by the vaccine-developing country-specific National Regulatory Authority (NRA). In addition, 100–150 vaccines are under various phases of pre-clinical and clinical trials. The mainstay of global vaccination is to introduce herd immunity, which would protect the majority of the population, including immunocompromised individuals, from infection and disease. Here, we primarily discuss category-wise vaccine development, their respective advantages and disadvantages, associated efficiency and potential safety aspects, antigenicity of SARS-CoV-2 structural proteins and immune responses to them along with the emergence of SARS-CoV-2 VOC, and the urgent need of achieving herd immunity to contain the pandemic.

Exploring the Immunomodulatory Aspect of Mesenchymal Stem Cells for Treatment of Severe Coronavirus Disease 19

“…However, in certain cases, the activated immune response turns potentially pathological rather than protective, thereby causing dreadful and fatal health conditions like acute respiratory distress syndrome (ARDS), and eventual death. Therefore, the collective global fight against COVID-19, based on an array of effective interventions, including drug repurposing [ 128 , 129 ], antibody cocktail [ 130 , 131 ], vaccine [ 52 ], and stem cell-based therapy [ 132 ], are urgently required to millions of lives. This challenge is increasingly being compounded owing to the origin of various SARS-CoV-2 variants of concerns with enhanced intrinsic pathogenic properties [ 133 ].…”

“…SARS-CoV-2 virion consists of a single RNA molecule, several accessory factors, and four categories of structural proteins: namely, spike (S), membrane (M), envelope (E), and nucleocapsid (N). These structural proteins intrinsically possess differential levels of immunogenicity [ 52 ], thereby eliciting a varied extent of immune responses with considerably different clinical consequences. Therefore, such structural proteins, especially glycosylated trimeric S protein [ 53 ] owing to its prominent immunogenic nature and crucial determinant of infection, are also the target for therapeutic intervention, apart from several host-derived cellular factors [ 54 ].…”

Evaluation of anti-spike glycoprotein antibody and neutralizing antibody response of different vaccine platforms. A protocol of systematic review and meta-analysis of COVID-19 vaccine clinical trial studies

“…Given the critical need for pandemic control, efforts have been made to formulate high-performance vaccines with the maximum effective immune response and minimal side effects (28,29). So far, various prophylactic vaccines with different efficacy and safety have been approved for the COVID-19, depending on their structure and ability to elicit immune responses (30)(31)(32)(33). Multiple preclinical and clinical trial studies have been conducted or are underway to examine various aspects of COVID-19 vaccine platforms (15,17,34).…”

4BNT162b2 mRNA COVID‐19 vaccine and semen: What do we know?

“…12,13 On the other hand, Chaudhary et al reported adverse reactions related to the use of vaccine excipients and/or adjuvants. 12 Previously, Xu et al studied the reproductive toxicity of adjuvants such as silver nanoparticles 14 in rabies virus vaccines and highlighted that their small size can allow crossing through biological barriers such as the blood-testis barrier, inducing cytotoxicity (inflammatory state and a decrease in mitochondrial function with the production of reactive oxygen species [ROS] and an increase in cellular apoptosis and/or a downregulation of gene expression, which could induce cellular apoptosis). Moreover, cytotoxicity has been associated with electrolyte imbalance between the intracellular membrane and the extracellular membrane, which leads to an alteration of metabolic activities.…”