|Year : 2020 | Volume
| Issue : 2 | Page : 70-72
COVID-19: An update on vaccine development
Deepak Tripathi, Guohua Yi, Ramakrishna Vankayalapati
Department of Pulmonary Immunology, Center for Biomedical Research, The University of Texas Health Science Center, Tyler, Texas, United States of America
|Date of Web Publication||29-May-2020|
Dr. Deepak Tripathi
Assistant Professor, Department of Pulmonary Immunology, Center for Biomedical Research, The University of Texas Health Science Center, Tyler, Texas, Tx 75708
United States of America
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Tripathi D, Yi G, Vankayalapati R. COVID-19: An update on vaccine development. Indian J Rheumatol 2020;15:70-2
COVID-19 caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which appeared in December 2019 in China. Till date, it has infected more than 2.87 million individuals and caused more than 202,000 deaths worldwide. Here, we highlighted the challenges for vaccine development for SARS-CoV-2. Newly developed COVID-19 vaccines will require careful safety evaluations to prevent the events that may lead to increased infectivity or inflammation. Several vaccines are being rapidly developed, and human trials begin at the first wave of this pandemic. Now, different vaccine strategies such as whole-virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines are under evaluation at clinical and preclinical stage. If SARS-CoV-2 establishes in the community population, a vaccine will be essential to provide protection against COVID-19.
| Coronavirus Vaccine Design|| |
Vaccine technology has significantly improved in the last few years. Structural biology helps in the development of several RNA and DNA vaccine candidates, licensed vectored vaccines, recombinant protein vaccines, and cell-culture-based vaccines. Genomic map of SARS-CoV-2 was identified in a short time frame, and its genomic sequences made widely available by researchers. From experience of previous vaccine studies on SARS-CoV-1 and Middle East respiratory syndrome-coronavirus (MERS-CoV), it is known that the S-protein on the surface of the virus is a suitable target for vaccine design. This S-protein interacts with the receptor angiotensin I-converting enzyme 2 (ACE2). The complete structure of the S-protein from SARS-CoV-2 is now available, and it is being explored for vaccine target. This vaccine candidate can be incorporated into advanced vaccine platforms. Previously, recombinant S-protein-based vaccines, attenuated and whole-inactivated vaccines, and vectored vaccines for SARS-CoV-1 were tested in preclinical models.,, These vaccines were effective but not able to induce sterilizing immunity. Some live virus-based vaccines induce severe complications such as granulocyte infiltration and lung and liver injuries. Studies from S-protein based vaccines have been demonstrated that epitopes on the S-protein are protective however few epitopes aggravate the disease. Overall, vaccination was associated with better protection along with minor complications.
An effective coronavirus vaccine should be designed in a manner to induce an optimal antibody response. It has been shown that coronavirus-infected individuals with mild or no symptoms do not induce long-lived antibody responses,, and there is a chance of reinfection with the same virus in an extended time period. Individuals infected with SARS-CoV-1 or MERS-CoV had a very low level of antibody titer within 2–3 years, which suggests that infected individuals also have a chance of infections within few years. Therefore, an effective SARS-CoV-2 vaccine will need to design to minimize these issues and protect when the virus causes seasonal epidemics.
SARS-CoV-2 mostly displays severe pathology in the elderly (above 70 years of age) and individuals with comorbidities, but the exact reason is unknown. It is very important to develop a vaccine that is able to provide protection in the elderly because this segment of population typically responds less against vaccination because of immune senescence. If vaccination works in younger individuals and stops transmission in the community, it may provide an indirect benefit to elderly individuals. Few SARS-CoV-1 vaccines did not progress beyond Phase 1 clinical trial because of lack of funding. Mostly, these vaccines were S-protein-based DNA and inactivated virus-based vaccine and were able to induce neutralizing antibody titers., Recent studies showed that neutralizing monoclonal antibodies isolated against SARS-CoV-1 can cross-react with the receptor-binding domains of the SARS-CoV2., Findings from these studies suggesting vaccines against SARS-CoV1 may be able to provide protection against SARS-CoV-2 but these vaccines still in Phase 1 trial. Many vaccines developed targeting MERS-CoV S-protein are also still in preclinical and clinical development., The chances are very minimal that MERS-CoV vaccines may induce strong cross-neutralizing antibodies to SARS-CoV2 because of the phylogenetic difference between these two viruses.,,
| Progress for Severe Acute Respiratory Syndrome-Coronavirus-2 Vaccines|| |
The major hurdle to develop vaccines for human use in a short time frame is that novel technologies used to generate these vaccines have not been extensively tested for safety or scaled up to mass production. It may take a significant amount of time to resolve these issues first time. According to the World Health Organization, 70 coronavirus vaccines are under development, with 3 in clinical trials. The first coronavirus vaccine trial has been started by the Kaiser Permanente Washington Health Research Institute. This vaccine is known as mRNA-1273 and was developed by the National Institute of Allergy and Infectious Diseases scientists and their collaborators at the biotechnology company Moderna, Inc., based in Cambridge, Massachusetts. The Coalition for Epidemic Preparedness Innovations supported the manufacturing of the vaccine candidate for the Phase 1 clinical trial., Recently, another adenovirus containing S-protein vaccine ChAdOx1nCoV-19 came for clinical trial in record time. This vaccine developed by a research group in Jenner Institute at Oxford University in partnership with the UK-based global biopharmaceutical company AstraZeneca. Many academic and industry-based research groups are working on recombinant protein-based approach and mainly focusing on S-protein, viral vector-based vaccines, DNA vaccines, live attenuated vaccines (Serum Institute of India with Codagenix), and inactivated virus vaccines. The major concerns about the current vaccine designs are whether they will be effective due to the high frequency of glycosylation and mutations in the S- protein, as well as the potential antibody-dependent enhancement.
In vaccine development process, appropriate animal models are very critical to test protective responses. SARS-CoV2 does not grow in wild-type animals and induce mild disease in transgenic animals expressing ACE2. Another suitable model will be nonhuman primate, for which pathogenicity studies are going on at a primate center of Texas Biomedical Research Center at San Antonio, USA. If a vaccine with optimal efficacy is generated, the next challenge will be the large-scale production of vaccine with good manufacturing practice to ensure the quality and safety.
| Conclusion|| |
In the future, the next coming months will be very critical to develop an effective vaccine or therapeutic options to battle with this pandemic. Lesson from this pandemic is that it would be the right time to consider investing in the development of better vaccine technologies that help to develop a protective vaccine as quickly as possible. In addition, we need to develop a better emergency plan that would allow us to produce and distribute vaccines within a short time frame.
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