Covid-19: the search for a vaccine – analysis
Pandemics are most often surprising mainly due to deforestation, environmental degradation, rapid urbanization, overpopulation, migration, and growing animal and human conflict. There is no herd or population immunity against new pathogens such as Sars-Cov-2 that causes coronavirus disease (Covid-19), and until herd or population immunity crosses 70%, it will continue to spread. In these circumstances, public health interventions in combination with an effective vaccine can mitigate the situation.
India has the distinction of creating a vaccine for a new virus decades ago, when Kyasanur forest disease was first reported from the Shimoga district of Karnataka and is now endemic in Karnataka, Kerala, Maharashtra and Goa. This vaccine, although raw, is used even today. Shantha Biotech has manufactured the world’s first effective oral cholera vaccine. The vaccine has not been used in India because cholera outbreaks are rare, but it is used worldwide in emergency situations, including in Haiti and Myanmar.
The speed with which the Covid-19 pandemic progresses leaves the world with no choice but to have an emergency use vaccine ready within six to eight months. We cannot afford to wait for years. In the past, the Ebola vaccine was quickly made available. The world already has some experience with coronavirus vaccines against the viruses that cause Severe Acute Respiratory Syndrome (Sars) and Middle East Respiratory Syndrome (Mers). The proven platforms and plugins used for vaccine development are established and have been used to administer other vaccines. Since we are not starting from scratch, an early shot is possible.
Most vaccines are being developed to provide immune responses, either using pre-fusion or full-peak protein. The antigen is expressed in the human body through messenger RNA or DNA (genetic material) placed through a carrier or placed on a platform.
When injected into humans, the antigen is expressed and generates an immune response. Before antigens are placed on platforms, they are tested against convalescent plasma and monoclonal antibodies in vitro, ex vivo, or in vivo. Experiments with mice and monkeys are also carried out. Since none of these is available in India, Indian companies are outsourcing to international companies or laboratories.
Special phantom cell assays are also needed to analyze neutralizing antibodies to detect adverse reactions in cells taken from the lungs or bronchi.
The most promising vaccine is the LPN-RNA (messenger RNA) vaccine developed by Moderna, who completed her Phase I trial with Emory’s help and began recruiting for Phase II. Phase I data for this two-dose vaccine, administered 29 days apart, are under analysis. Pfizer’s four messenger RNA vaccine with BNTECH also went into Phase I / II testing.
In India, Gennova Pharmaceuticals has developed and patented a messenger RNA vaccine for use with a lipid iron oxide (LION) carrier and an adjuvant known as GLA-SE. Convalescent serum experiments and challenge studies with mice and monkeys have obtained very high neutralizing antibody titers.
A DNA vaccine developed by INOVIO Pharmaceuticals was tested in South Korea. In association with Cadila Pharmaceuticals in India, Novavax, based in the USA. The US is using the virus-like particle platform (VLP), which has previously been used for the papillomavirus vaccine. With this platform, the company has marketed seasonal flu, H1N1 and rabies vaccines in India. This vaccine is also in phase I testing in the United States (USA) and Australia.
The University of Oxford is using an adenovirus platform for chimpanzees to develop a vaccine, which will be manufactured by AstraZeneca in Europe and the Serum Institute in India. It is in the testing phase of Phase I. Johnson & Johnson is using the adeno-26 platform and the pre-fusion protein, which has been used successfully in Ebola and RSV vaccine trials. This platform is not being used by any company in India.
Aurobindo has bought a small startup from Pfizer in the United States and is using a vesicular stomatitis virus platform for vaccine development, which will likely be manufactured at its unit in Hyderabad. The other fast-moving projects in India are the CSIR-funded CCMB-Bharat Biotech association, which uses a dead vaccine for which the strain was obtained from the National Institute of Virology, Pune. Zydus-Cadila in India is also struggling with a measles virus platform. Other projects are using an attenuated viral vaccine, which is similar to vaccines being developed in China. Immunoglobulins against Covid-19 antigen specific epitopes will come before vaccines are only available in Israel and a cocktail of 3 is available in the United States and undergo testing (these provide passive vaccination).
There are currently more than 110 vaccine projects underway, and developers are taking unprecedented approaches. Emergency use of the vaccine is administered as soon as Phase II and Phase III are complete, and mass manufacturing begins to assume the risk of Phase III failure. The countries in which they are located often finance risk reduction and offer market commitments. This has never happened before.
One of the challenges will be determining who will be vaccinated first. There are several scenarios, one of them is to vaccinate front-line workers, doctors, health workers, sanitation and delivery. The second scenario is to give them to children, and the last is to carry out ring vaccination around the critical points to immunize all contacts and the asymptomatic. The World Health Organization will provide guidance on this matter.
Even when we have a vaccine, public health measures will be equally important, such as avoiding risky behaviors, maintaining social distancing, working on nutrition and access to poor populations, and creating a mechanism to avoid the transmission of animals and humans.
If the trials fail and there is no vaccine available in time worldwide, the world will have to live with this disease for a long time.
Dr. NK Ganguly is the former CEO of the Indian Council of Medical Research.
The opinions expressed are personal.