Vaccines

The strange coronavirus outbreak in the Chinese city Wuhan, now termed COVID-19, and its rapid transmission, threatens people around the world. Because of its pandemic nature, the National Institutes of Health (NIH) and pharmaceutical companies are involved in the development of COVID-19 vaccines. Xu Nanping, China's vice minister of science and technology, announced that the first vaccine is expected to be ready for clinical trials in China at the end of April 2020. There is no approved vaccine or treatment for COVID-19 infections till now.

Vaccine development is sponsored and supported by Biomedical Advanced Research and Development Authority (BARDA), a component of the Office of the Assistant Secretary for Preparedness and Response (ASPR). Sanofi will use its egg-free, recombinant DNA technology to produce an exact genetic match to the proteins of this virus.

The S protein plays a significant role in the induction of protective immunity against SARS-CoV by mediating T-cell responses and neutralizing antibody production. In the past few decades, we have seen several attempts to develop a vaccine against human coronaviruses by using S protein as the target. However, the developed vaccines have minimal application, even among closely related strains of the virus, due to a lack of cross-protection. That is mainly because of the extensive diversity existing among the different antigenic variants of the virus. The contributions of the structural proteins, like spike (S), matrix (M), small envelope (E), and nucleocapsid (N) proteins, of SARS-CoV to induce protective immunity has been evaluated by expressing them in a recombinant parainfluenza virus type 3 vector (BHPIV3). Of note, the result was conclusive that the expression of M, E or N proteins without the presence of S protein would not confer any noticeable protection, with the absence of detectable serum SARS-CoV-neutralizing antibodies. Antigenic determinant sites present over S and N structural proteins of SARS-CoV-2 can be explored as suitable vaccine candidates. In the Asian population, S, E, M and N proteins of SARS-CoV-2 are being targeted for developing subunit vaccines against COVID-19.

The identification of the immunodominant region among the subunits and domains of S protein is critical for developing an effective vaccine against the coronavirus. The C-terminal domain of the SI subunit is considered the immunodominant region of the porcine deltacoronavirus S protein. Similarly, further investigations are needed to determine the immunodominant regions of SARS-CoV-2 for facilitating vaccine development.

However, our previous attempts to develop a universal vaccine that is effective for both SARS-CoV and MERS-CoV based on T-cell epitope similarly pointed out the possibility of cross-reactivity among coronaviruses. That can be made possible by selected potential vaccine targets that are common to both viruses. SARS-CoV-2 has been reported to be closely related to SARS-CoV. Hence, knowledge and understanding of S protein-based vaccine development in SARS-CoV will help to identify potential S protein vaccine candidates in SARS-CoV-2. Therefore, vaccine strategies based on the whole S protein, S protein subunits, or specific potential epitopes of S protein appear to be most promising vaccine candidates against coronavirus. The RBD of the SI subunit of S protein has a superior capacity to induce neutralizing antibodies. This property of the RBD can be utilized for designing potential SARS-CoV vaccines either by using RBD-containing recombinant proteins or recombinant vectors that encode RBD. Hence, the superior genetic similarity existing between SARS-CoV-2 and SARS-CoV can be utilized to repurpose vaccines that have proven in vitro efficacy against SARS-CoV to be utilized for SARS-CoV-2. The possibility of cross-protection in COVID-19 was evaluated by comparing the S-protein sequences of SARS-CoV-2 with that of SARS-CoV. The comparative analysis confirmed that the variable residues were found concentrated on the SI subunit of S protein, an important vaccine target of the virus. Hence, the possibility of SARS-CoV-specific neutralizing antibodies providing cross-protection to COVID-19 might be lower. Further genetic analysis is required between SARS-CoV-2 and different strains of SARS-CoV and SARS-like (SL) CoVs to evaluate the possibility of repurposed vaccines against COVID-19. This strategy will be helpful in the scenario of an outbreak, since much time can be saved, because preliminary evaluation, including in vitro studies, already would be completed for such vaccine candidates. Multiepitope submit vaccines can be considered a promising preventive strategy against the ongoing COVID-19 pandemic. In silico and advanced immunoinformatic tools can be used to develop Multiepitope subunit vaccines. The vaccines that are engineered by this technique can be further evaluated using docking studies and, if found effective, then can be further evaluated in animal models. Identifying epitopes that have the potential to become a vaccine candidate is critical to develop an effective vaccine against COVID-19. The immunoinformatics approach has been used for recognizing essential epitopes of cytotoxic T lymphocytes and B cells from the surface glycoprotein of SARS-CoV-2. Recently, a few epitopes have been recognized from the SARS-CoV-2 surface glycoprotein. The selected epitopes explored targeting molecular dynamic simulations, evaluating their interaction with corresponding major histocompatibility complex class I molecules. They potentially induce immune responses. The recombinant vaccine can be designed by using rabies virus (RV) as a viral vector. RV can be made to express MERS-CoV S1 protein on its surface so that an immune response is induced against MERS-CoV. The RV vector-based vaccines against MERS-CoV can induce faster antibody response as well as higher degrees of cellular immunity than the Gram-positive enhancer matrix (GEM) particle vector based vaccine. However, the latter can induce a very high antibody response at lower doses. Hence, the degree of humoral and cellular immune responses produced by such vaccines depends upon the vector used.

Dual vaccines have been getting more popular recently. Among them, the rabies virus-based vectored vaccine platform is used to develop vaccines against emerging infectious disease. The dual vaccine developed from inactivate rabies virus particles that express the MERS-CoV S1 domain of S protein was found to induce immune responses for both ERS-CoV and rabies virus. The vaccinated mice were found to be completely protected from challenge with MERS-CoV.