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Fighting from the Frontline: In Conversation with Dr. Shweta Jindal – The COVID-19 Oxford Vaccine Trial Explained

Dr. Shweta Jindal (MBBS, MD, MRCPH) is an MTI Fellow of Paediatric Critical Care, Oxford University. She speaks to Devadeep Chowdhury about the groundbreaking vaccine trial her alma mater is presently indulged in and has given real hope for a vaccine for COVID-19.


Q. The Oxford trial for a vaccine for COVID-19 has reportedly triggered an immune response. Can you explain what it means? How significant is it?

A. Yes, indeed, there is reassuring news following the publication of the Oxford SARS-CoV-2 vaccine trials in Lancet, which is one of the most highly accredited medical journals across the world. 

This vaccine, named as ChAdOx1 nCoV-19, has been proven to be safe and effective during Phases-1 and 2 of clinical trials. The name comes from the origin of the vaccine – it is a mutated chimpanzee adenovirus strain that causes the common cold in animals. This has been genetically modified to present the spike protein of the SARS-CoV-2 virus, which acts as the mode of entry into the host cells. 

The study suggests that during the initial trials on over 1000 human volunteers, the vaccine has shown to generate a dual immune response against the SARS-CoV-2 virus. A dual response means that it is able to generate both cellular and humoral immunity against the virus – which is a distinguishing feature of this vaccine, compared to all other current candidates under trial. 

This is a positive finding in terms of the scope of the vaccine, as it is able to offer a better immune response by stimulating the production of T-cells (which are a type of protective white blood cells produced in response to infections) and antibodies (which are produced from B-cells, another defense mechanism of the body against infections). 

After a vaccine has been produced and tested in pre-clinical trials (on animals and in vitro), Phases 1 and 2 of clinical trials are meant to test the safety and effectiveness of a vaccine and help determine an effective dose – which has been completed in this case. This is quite a significant achievement since this is the first vaccine to be at this stage among the other candidates being tested at labs in the US, China, Russia, and India. 


Q. What are the next possible steps on this trial? 

A. The next steps are proceeding to Phase-3 (and 4) of clinical trials. The ChAdOx1 vaccine is set for this trial on around 30,000 people and will be tested in various populations, including countries like the US, India, Brazil, and Mexico. 

During Phase-3, a vaccine is tested on a larger group of people to determine the efficacy (which is different from effectiveness) of it, and if it triggers any serious adverse effects which might be rare and hence discovered only when given to a larger number of people. The efficacy of a vaccine means to what extent it is able to protect the intended population, and which subsets of people are more (or less) likely to benefit from it. 

Once this is completed, the vaccine is marketed and distributed for large-scale use and followed up for quality control and post-marketing surveillance for rare adverse effects. Usually, once Phase-3 is successfully completed, it is safe to consider that a vaccine can be distributed for usage in the intended population.


Q. Can you make an assumption on how long will take for this vaccine, if successful, to be made available for mass usage?

A. In normal circumstances, it can take years for successful completion of clinical trials of a vaccine, following which it is made available for mass usage. 

This includes the time taken in the recruitment of volunteers for these trials, administering the vaccine, observing them for its effects, collection of data on response and adverse effects, and analyzing that data to determine the efficacy and incidence of serious adverse effects. It is not as straightforward a process though since researchers need to bear in mind a number of factors such as comorbidities, immune status of individuals, and ensure inclusion of groups likely to benefit most from a vaccine (for example, frontline workers and elderly individuals in the case of COVID-19). 

However, due to the nature of the pandemic and the urgency of the situation, this has already been accelerated with the help of organizations like WHO (World Health Organization) and partners, by launching the ACT accelerator (Access to COVID-19 Tools). As a result of these efforts, we have been able to see an exceptional pace of development of vaccines with these phases being completed in less than six months. 

The phases ahead are the ones that take anywhere between six to nine months to complete, not including the time spent in operationalizing and delivering the vaccine at the usage sites. This is where governments and partners like the United Nations International Children’s Fund (UNICEF) and Gavi, The Vaccine Alliance would have a significant role – to start preparing for vaccine delivery so that the process can be expedited. This can be achieved by: 

  • Having a regulatory standard and clear criteria for vaccine candidates to advance through the various stages
  • Preparing a strategy and policy for deployment among the various risk groups
  • Investing in community engagement and preparedness

Q. As a former Oxford fellow, how would you rate their efforts so far? Can you give us an idea of how this exercise was carried out?

A. I have been fortunate enough to spend time with some of the investigators involved in this trial during my fellowship in Paediatric Critical Care at Oxford. Professor Pollard, who is a part of the Department of Infectious Diseases, for example, is a highly experienced and knowledgeable resource when it comes to such a topic. 

As someone who has closely witnessed the quality and rigor of research at the university, I feel very happy about this significant trial which has brought joy to not only those involved in the research, but also the masses across the world who have been waiting with bated breath for these reassuring developments. The report that has been published in Lancet reflects not only the dedication of the researchers but also the novelty in approach (which may account for the exceptional response to the study). 

The vaccine was developed after preliminary research on the effectiveness of a similar vaccine in monkeys but against another kind of flu. Based on the findings, the team proposed to genetically modify the ChAdOx1 virus so that it can present the antigen in the spike protein of SARS-CoV-2, which the virus uses to gain entry into the host cells. The vaccine was manufactured according to current Good Manufacturing Practice by the Clinical BioManufacturing Facility (University of Oxford, Oxford, UK). 

The pre-clinical phases were followed up by recruitment of healthy human volunteers aged 18-55 years, excluding those with history of laboratory-confirmed SARS-CoV-2 infection and those at higher risk for SARS-CoV-2 exposure pre-enrolment (i.e., front-line health-care workers working in emergency departments, intensive care units, and COVID-19 wards, and close contacts of confirmed COVID-19 cases). 

After the recruitment of 1077 participants, they were divided randomly into two arms of cases and controls – who would receive an unrelated vaccine for comparison. A single intramuscular dose of the vaccine was administered to the subjects, and they were observed for immune response and adverse effects over the next four weeks. 

Cellular immune response was found to peak at two weeks, followed by an antibody response at four weeks from the vaccine administration. Local and systemic reactions – including pain, fever, chills, muscle ache, headache, and malaise – were reduced by the use of prophylactic paracetamol. There were no serious adverse events related to ChAdOx1. 

All five centers of the trial reported a correlation in their findings and sustained immune response to the vaccine tested using multiple techniques. 


Q. What are the implications of these developments for the masses?

A. While these developments are indeed hopeful and instill positivity amidst all in these trying times, we must remember that it is a long road from the development of a vaccine to its availability. 

Vaccine development and delivery is a process involving multiple steps, including preparing the logistics and supply chain management while dealing with a complicated local policy environment. As in the case of any health policy decision, economic factors such as cost-effectiveness analysis are also taken into account. 

It has been anticipated that the vaccine is more likely to be made available for administration to those at the highest risk, and, thus, most likely to benefit from it. 

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