Indian Journal of Rheumatology

: 2020  |  Volume : 15  |  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

Correspondence Address:
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

How to cite this article:
Tripathi D, Yi G, Vankayalapati R. COVID-19: An update on vaccine development.Indian J Rheumatol 2020;15:70-72

How to cite this URL:
Tripathi D, Yi G, Vankayalapati R. COVID-19: An update on vaccine development. Indian J Rheumatol [serial online] 2020 [cited 2022 Jan 28 ];15:70-72
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Full Text

COVID-19 caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which appeared in December 2019 in China.[1] Till date, it has infected more than 2.87 million individuals and caused more than 202,000 deaths worldwide.[2] 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.[3] Genomic map of SARS-CoV-2 was identified in a short time frame, and its genomic sequences made widely available by researchers.[4] 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).[5] The complete structure of the S-protein from SARS-CoV-2 is now available, and it is being explored for vaccine target.[6] 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.[7],[8],[9] 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.[10] 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.[11]

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,[12],[13] and there is a chance of reinfection with the same virus in an extended time period.[14] Individuals infected with SARS-CoV-1 or MERS-CoV had a very low level of antibody titer within 2–3 years,[15] 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.[16] 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.[9] Mostly, these vaccines were S-protein-based DNA and inactivated virus-based vaccine and were able to induce neutralizing antibody titers.[9],[17] Recent studies showed that neutralizing monoclonal antibodies isolated against SARS-CoV-1 can cross-react with the receptor-binding domains of the SARS-CoV2.[18],[19] 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.[20],[21] 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.[20],[22],[23]

 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.[24],[25] 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.[26] 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.


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.


1Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. J Adv Res 2020;24:91-8.
2COVID-19 Situation Reports. Available from: [Last accessed on 2020 May 01].
3Anasir MI, Poh CL. Structural Vaccinology for Viral Vaccine Design. Front Microbiol 2019. p. 10. Available from: 2019.00738/full. [Last accessed on 2020 May 01].
4Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020;395:565-74.
5Sanche S, Lin YT, Xu C, Romero-Severson E, Hengartner N, Ke R. Early release-High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus. Emerging Infect Dis J 2020;26. Available from: [Last accessed on 2020 Apr 29].
6Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S. The spike protein of SARS-CoV – A target for vaccine and therapeutic development. Nat Rev Microbiol 2009;7:226-36.
7Deming D, Sheahan T, Heise M, Yount B, Davis N, Sims A, et al. Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants. PLoS Med 2006;3:e525.
8Tseng CT, Sbrana E, Iwata-Yoshikawa N, Newman PC, Garron T, Atmar RL, et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One 2012;7:e35421.
9Jiang S, He Y, Liu S. SARS vaccine development. Emerg Infect Dis 2005;11:1016-20.
10Khoury M, Cuenca J, Cruz FF, Figueroa FE, Rocco PR, Weiss DJ. Current status of cell-based therapies for respiratory virus infections: Applicability to COVID-19. Eur Respir J 2020;2000858. Available from: [Last accessed on 2020 Apr 29].
11Enjuanes L, Dediego ML, Alvarez E, Deming D, Sheahan T, Baric R. Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease. Virus Res 2008;133:45-62.
12Peng H, Yang LT, Wang LY, Li J, Huang J, Lu ZQ, et al. Long-lived memory T lymphocyte responses against SARS coronavirus nucleocapsid protein in SARS-recovered patients. Virology 2006;351:466-75.
13Martin JE, Louder MK, Holman LA, Gordon IJ, Enama ME, Larkin BD, et al. A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial. Vaccine 2008;26:6338-43.
14Bao L, Deng W, Gao H, Xiao C, Liu J, Xue J, et al. Reinfection could not occur in SARS-CoV-2 infected rhesus macaques. bioRxiv 2020.03.13.990226; 2020.
15Okba NM, Müller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, et al. Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease 2019 patients. Emerg Infect Dis 2020;26.
16Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62.
17Amanat F, Krammer F. SARS-CoV-2 Vaccines: Status Report. Immunity; 2020. Available from: [Last accessed on 2020 Apr 29].
18Berry JD, Hay K, Rini JM, Yu M, Wang L, Plummer FA, et al. Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology. MAbs 2010;2:53-66.
19Jiang S, Hillyer C, Du L. Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Trends Immunol 2020;41:355-9. Available from: [Last accessed on 2020 Apr 29].
20Schindewolf C, Menachery VD. Middle east respiratory syndrome vaccine candidates: Cautious optimism. Viruses 2019;11:74. Available from: [Last accessed on 2020 Apr 29].
21Cho H, Excler JL, Kim JH, Yoon IK. Development of middle east respiratory syndrome coronavirus vaccines-advances and challenges. Hum Vaccin Immunother 2018;14:304-13.
22Chan JF, Lau SK, To KK, Cheng VC, Woo PC, Yuen KY. Middle East respiratory syndrome coronavirus: Another zoonotic betacoronavirus causing SARS-like disease. Clin Microbiol Rev 2015;28:465-522.
23Wang L, Shi W, Joyce MG, Modjarrad K, Zhang Y, Leung K, et al. Evaluation of candidate vaccine approaches for MERS-CoV. Nat Commun 2015;6:7712. [Last accessed on 2020 Apr 29].
24NIH Clinical Trial of Investigational Vaccine for COVID-19 Begins,NIH: National Institute of Allergy and Infectious Diseases. Available from: nical-trial-investigational-vaccine-covid-19-begins. [Last accessed on 2020 Apr 29].
25Moderna Ships mRNA Vaccine Against Novel Coronavirus (mRNA-1273) for Phase 1 Study. Moderna, Inc. Available from: ews-releases/news-release-details/moderna-ships-m rna-vaccine-against-novel-corona virus-mrna-1273. [Last accessed on 2020 Apr 29].
26Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med 2020;S0953-6205(20)30151-5. Available from: [Last accessed on 2020 Apr 29].