New insights on possible vaccine development against SARS-CoV-2

International Journal of Pathogen Research, 2020

In time past, to date combating against diseases and fatal disorders (of known or idiopathic cause) is a major effort among the human race. The emergence of several, novel and pathogenic viral infections have posed a great threat to humanity and could wipe us out of existence if there are no counter measures. Among the increasing number of pathogenic viruses in this past decade, the advent of the recent imperial SARS-CoV-2 coronavirus type cannot be underestimated as it is not just a malady endemic to a nation, but have also triggered an emergency of public health across the globe. SARS-CoV-2 a memorial of the initial Severe Acute Respiratory Syndrome (SARS) reported in China in (2003) is the etiological agent of the mysterious COVID-19 reported to originate from Wuhan, Hubei province, China in 2019. Though the virus exhibit mild pathogenicity compared to other previously emerged human coronaviruses (HCoV-OC43, HCoV-HKU1, MERS-CoV, and SARS-CoV), however, the high transmissibility and infectivity among human is alarming. In spite the evidences from the increasing number of substantiated global cases and deaths resulting from the epidemic outbreak to date, curative measures to curtail and treat this disease are still lacking. Just like SARS-CoV, it has been revealed that SARS-CoV-2 also uses similar receptor for infectivity and shares similar disease pathogenesis. This knowledge presents a therapeutic target against COVID-19. The presence of cross-reactive epitopes in the spike protein subunit of SARS-CoV and SARS-CoV-2 present the use of neutralization antibodies from convalescent SARS challenged patients against COVID 19. However, limited cross-neutralization due to lower sequence conservation in the Spike protein subunit could render this approach ineffective. Realizing the urgent need for developing potent therapeutics against the imminent risk of COVID-19 on humanity, this review article, suggests the use of SARS-CoV-2 recombinant Spike protein-based vaccine as an immunotherapeutic target to combat COVID-19 based on garnered knowledge from researches on consanguineal coronaviruses (SARS-CoV, and MERS-CoV), and current trends in vaccine development against this infection.

Frontiers in Immunology, 2021

Coronavirus 19 Disease (COVID-19) originating in the province of Wuhan, China in 2019, is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), whose infection in humans causes mild or severe clinical manifestations that mainly affect the respiratory system. So far, the COVID-19 has caused more than 2 million deaths worldwide. SARS-CoV-2 contains the Spike (S) glycoprotein on its surface, which is the main target for current vaccine development because antibodies directed against this protein can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. However, the emergence of new SARS-CoV-2 variants could affect the effectiveness of vaccines. Here, we review the different types of vaccines designed and developed against SARS-CoV-2, placing emphasis on whether they are based on the...

Frontiers in Immunology, 2021

The newly emerged novel coronavirus, SARS-CoV-2, the causative agent of COVID-19 has proven to be a threat to the human race globally, thus, vaccine development against SARS-CoV-2 is an unmet need driving mass vaccination efforts. The receptor binding domain of the spike protein of this coronavirus has multiple neutralizing epitopes and is associated with viral entry. Here we have designed and characterized the SARS-CoV-2 spike protein fragment 330-526 as receptor binding domain 330-526 (RBD330-526) with two native glycosylation sites (N331 and N343); as a potential subunit vaccine candidate. We initially characterized RBD330-526 biochemically and investigated its thermal stability, humoral and T cell immune response of various RBD protein formulations (with or without adjuvant) to evaluate the inherent immunogenicity and immunomodulatory effect. Our result showed that the purified RBD immunogen is stable up to 72 h, without any apparent loss in affinity or specificity of interactio...

npj Vaccines

The new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.

ACS Central Science

The development of recombinant COVID-19 vaccines has resulted from scientific progress made at an unprecedented speed during 2020. The recombinant spike glycoprotein monomer, its trimer, and its recombinant receptorbinding domain (RBD) induce a potent anti-RBD neutralizing antibody response in animals. In COVID-19 convalescent sera, there is a good correlation between the antibody response and potent neutralization. In this review, we summarize with a critical view the molecular aspects associated with the interaction of SARS-CoV-2 RBD with its receptor in human cells, the angiotensin-converting enzyme 2 (ACE2), the epitopes involved in the neutralizing activity, and the impact of virus mutations thereof. Recent trends in RBD-based vaccines are analyzed, providing detailed insights into the role of antigen display and multivalence in the immune response of vaccines under development.

Nature Communications

The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd protection and control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) from the full-length spike (S) protein that is stable in the prefusion conformation. NVX-CoV2373 S form 27.2-nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicit high titer anti-S IgG that blocks hACE2 receptor binding, neutralize virus, and protects against SARS-CoV-2 challenge with no evidence of vaccine-associated enhanced respiratory disease. NVX-CoV2373 also elicits multifunctional CD4+ and CD8+ T cells, CD4+ follicular helper T cells (Tfh), and antigen-specific germinal center (GC) B cells in the spleen. In baboons, low-dose levels of NVX-CoV2373 with Matrix-M was also h...

Iranian Journal of Public Health

COVID-19 is considered as the third human coronavirus and has a high potential for transmission. Fast public health interventions through antibodies, anti-virals or novel vaccine strategies to control the virus and disease transmission have been extremely followed. SARS-CoV-2 shares about 79% genomic similarity with SARS-CoV and approximately 50% with MERS-CoV. Based on these similarities, prior knowledge in treating SARS-CoV and MERS-CoV can be used as the basis of majority of the alternatives for controlling SARS-CoV-2. Immunotherapy is an effective strategy for clinical treatment of infectious diseases such as SARS-CoV-2. Passive antibody therapy, which decreases the virus replication and disease severity, is assessed as an effective therapeutic approach to control SARS-CoV-2 epidemics. The close similarity between SARS-CoV-2 genome with the SARS-CoV genome caused both coronaviruses to bind to the same angiotensin-converting enzyme 2 (ACE2) receptors that found in the human lung....

Journal of Translational Medicine, 2020

COVID-19 has rapidly spread all over the world, progressing into a pandemic. This situation has urgently impelled many companies and public research institutes to concentrate their efforts on research for effective therapeutics. Here, we outline the strategies and targets currently adopted in developing a vaccine against SARS-CoV-2. Based on previous evidence and experience with SARS and MERS, the primary focus has been the Spike protein, considered as the ideal target for COVID-19 immunotherapies.

International Journal of Molecular Sciences

Background: The recent COVID-19 pandemic produced a significant increase in cases and an emergency state was induced worldwide. The current knowledge about the COVID-19 disease concerning diagnoses, patient tracking, the treatment protocol, and vaccines provides a consistent contribution for the primary prevention of the viral infection and decreasing the severity of the SARS-CoV-2 disease. The aim of the present investigation was to produce a general overview about the current findings for the COVID-19 disease, SARS-CoV-2 interaction mechanisms with the host, therapies and vaccines’ immunization findings. Methods: A literature overview was produced in order to evaluate the state-of-art in SARS-CoV-2 diagnoses, prognoses, therapies, and prevention. Results: Concerning to the interaction mechanisms with the host, the virus binds to target with its Spike proteins on its surface and uses it as an anchor. The Spike protein targets the ACE2 cell receptor and enters into the cells by usin...

American Journal of Chemistry and Pharmacy

In December 2019, a mysterious pneumonia-causing sickness frightened the world. SARS-CoV-2 caused the acute respiratory illness. Since March 11, 2020, 220,563,227 COVID-19 cases and 4,565,483 deaths have been reported worldwide as of October 2021. SARS-CoV-2, like all coronavirus, appears to have crowns due to its S proteins and enters host cells using highly glycosylated spike (S) proteins. S1 and S2 are SARS-CoV-2 spike protein subunits. S2 controls transmembrane fusion, while S1 controls receptor binding. Antibody-mediated neutralization targets SARS-CoV-2 spike (S) proteins, which are essential for viral entry and fusion. This paper summarized how S protein was used in newly created and distributed SARS-CoV-2 vaccines and the implications for future advancements given the emergence of more lethal SARS-CoV-2 variants in this paper. It also discussed the role of S protein glycosylation in the viral entry and binding mechanism of SARS-CoV-2 and the implications for developing adapt...