Opinions

COVID-19 CHALLENGES IN VACCINE DEVELOPMENT-II

Hillol Das
Assam University
hilloldas.18@gmail.com

Recent Development of Corona Virus Vaccine

Many countries are in the race to introduce the first-ever novel coronavirus vaccine. Six months
into the global outbreak and trials are underway in laboratories around the world with several
companies and governments doubling their efforts to find a persistent solution for the deadly virus. In May, US pharmaceutical major Pfizer and its German partner BioNTech claimed that they have already initiated human trialing in the USA as well as in Germany. On the flip side, Remdesivir is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences which is being tested as a specific treatment for COVID-19 infections. The drug has been approved for emergency use in countries like the USA and Japan with a severe manifestation of
coronavirus infection. Later, pharmaceutical companies like Regeneron revealed that its ‘anti-body’ treatment drug could also be available.

Several other biopharmaceutical companies like Moderna, Johnson & Johnson have also geared
up attempts to design a COVID-19 vaccine. mRNA-1273 developed by Moderna based on prior
studies of related coronaviruses such as those that cause severe acute respiratory syndrome (SARS)
and the Middle East respiratory syndrome (MERS). It showed successfully neutralizing the
antibody titers in 8 participants who received either 25 µg or 100 µg doses. Moderna began
operating mRNA-1273 to patients in their Phase 2 trial on 29 May. The protocol is being finalized
for a Phase 3 trial of 30,000 volunteers, expected to start in July which is being funded by
Operation Warp Speed.

Unlike Moderna, Johnson & Johnson is working with Biomedical Advanced Research and
Development Authority (BARDA) and the company notified it had started pre-clinical testing on
various candidates in Boston and later disclosed that it had selected its lead vaccine candidate,
with two back-ups. Scientists at the Jenner Institute of Oxford University have affirmed to have
made a potential vaccine for coronavirus and the vaccine is being progressed with collective
partners including the Serum Institute of India.

A drug developed by biotech company Synairgen, Interferon Beta, has been administered in
patients as part of initial trials and the results of the Interferon Beta injection will be delivered by
June. Sanofi is leading upfront for developing a vaccine collaborating with Translate Bio under its
recombinant DNA manifesto using work from a previous SARS vaccine and measures that could
have both an instant and long-term impact. The company funded by BARDA plan to volunteer
patients in a Phase 1/2 trial in September.

Most recently India also shifted its gear in making the COVID 19 vaccine. India’s leading vaccine
development company, Bharat Biotech in collaboration with the Indian Council of Medical
Research (ICMR) and National Institute of Virology (NIV) has declared that India will probably
design an inactivated vaccine for COVID 19 candidate which they called as Covaxin expected to
begin in July. With the approval of DCGI (Drug Controller General of India) the indigenous,
inactivated vaccine is developed and manufactured in Bharat Biotech’s BSL-3 (Bio-Safety Level
3) high containment facility. Bharat Biotech is a reputed company and developed many vaccines
like rotavirus, hepatitis, Zika, Japanese encephalitis. The director-general of ICMR has lightened
on the fact by saying that the vaccine can be launched in the market for public use latest by August
15 after the vaccine completes all the mandatory clinical trials. Besides Covaxin, Bharat Biotech
is operating on two other vaccine candidates: one with the University of Wisconsin–Madison, and
FluGen, and the other with Thomas Jefferson University. As the virus threatens community spread,
there is a drastic need to ameliorate infrastructure, develop novel vaccine, assemble human
resources, support vanguard health workers and search for a remedy until the battle is
accomplished.

Presently, there is no immunogen available that can influence COVID-19 neutralizing antibodies.
So, there is a striking need to manufacture and dispense enough safe and effective vaccines that
can immunize an exceptionally huge number of individuals to protect the universal coterie from
the continued threat of medical issues and mortality from SARS-CoV-2. There is a global need for
vaccines to develop; and relating to the diversity of the pandemic, it requires more than one
effective vaccine approach.

What Is The Way Out?

Many vaccines work by eliciting a neutralizing Antibody (Abs) that prevents infection. However,
for some infectious agents, it has not been possible to create an efficacious vaccine, and for others,
the protection provided by vaccines is strain specific. When we are infected with any highly
mutating virus just like COVID-19, most of the antibodies we make are directed against the most
common epitope. Amino acids on these might vary from year to year, necessitating frequent
reformulation of the vaccine. In contrast, amino acid residues on the conserved domains are highly
conserved. Infected hosts rarely make antibodies against these domains. Nevertheless, broadly
neutralizing antibodies against these domains have been isolated that can block infection with
many different strains of the same viruses.

If we could design a vaccine that induces antibodies against these conserved motifs, it might confer
protection for many years. Strategies that aim to direct the immune system towards a particular
region of protein are referred to as “immunofocusing”. But these strategies have diverse drawbacks
too as they are not easily generalizable. Also, these immunofocussing techniques have low
resolution and difficulty to maintain the 3D structure of the epitope which is challenging. A
comprehensive understanding of the specific epitope recognized by the antibody is valuable not
only for antibody engineering but has also proven valuable knowledge for vaccine
design.

The collaboration will be crucial among biotechnology and pharmaceutical companies, many of
which are bringing forward a variety of vaccine approaches. The full development pathway for an
effective vaccine for SARS-CoV-2 will require that industry, government, and academia join
forces in unparalleled ways, each adding their strengths. This mechanism aims to initiate essential
safety and virtue data for several candidate vaccines in parallel, to quicken the endorsement and
distribution of multiple vaccine platforms and vaccines to protect against COVID-19 (coronavirus
disease 2019).

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