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Editorial
COVID‑19: An Update on Vaccine Development
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.[7‑9] 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
© 2020 Indian Journal of Rheumatology | Published by Wolters Kluwer - Medknow
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
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Tripathi, et al.: COVID-19 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.
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.
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
Address for correspondence:
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.
E‑mail: deepak.tripathi@uthct.edu
Received: May, 2020
Accepted: May, 2020
Published: May, 2020
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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.

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