The intricacies of vaccine science

Questions around emerging COVID-19 vaccines require a careful analysis of available data

February 16, 2021 12:05 am | Updated 12:05 am IST

Tamil Nadu, Chennai, 17/01/2021 : A vial of Covishield vaccine, developed by Oxford-Astrazeneca Plc. and manufactured by Serum Institute of India Ltd, picture taken at Government Royapettah Hospital in Chennai on Sunday. Photo: Jothi Ramalingam .B / The Hindu

Tamil Nadu, Chennai, 17/01/2021 : A vial of Covishield vaccine, developed by Oxford-Astrazeneca Plc. and manufactured by Serum Institute of India Ltd, picture taken at Government Royapettah Hospital in Chennai on Sunday. Photo: Jothi Ramalingam .B / The Hindu

Vaccine science is crucial for effective decision-making. For COVID-19, there are questions about different vaccines and platforms, their advantages, disadvantages, safety and efficacy, and the only way to address these questions is to consider the data and then make a call, while knowing that more data may lead to a change of practice.

Several news reports on February 13 stated that the government planned to stick to the “28-day gap” plan for the two doses of vaccines in India. This came just days after the World Health Organization (WHO) published its recommendations that for the AstraZeneca product, the gap between doses should be extended for as long as possible within an eight-to-12-week window.

Why did the WHO’s Strategic Advisory Group of Experts (SAGE) on immunisation make this recommendation? SAGE is generally conservative, relies on data and uses specific criteria for the strength of evidence to make its decision. So, what was the evidence and what should India do? On the other hand, why did Germany and other European countries decide not to use the AstraZeneca vaccine for older adults? And yet again, why are countries like France advising a single dose of vaccine for those who have had the SARS-CoV-2 infection? These are just a few questions where the data and the science behind decision-making need to be understood.

The information on AZD1222 vaccine (known as Covishield in India) provided to the WHO had a cut-off date of December 7, 2020. Based on data from 14,380 individuals from the U.K., Brazil and South Africa, who were at least two weeks beyond the second standard dose of vaccine, the vaccine had an efficacy of 63.1% against symptomatic COVID-19 infection (74 cases in the vaccinated group and 197 cases among controls). Two weeks after the second dose, there were eight cases of hospitalisation and three cases of severe infection, and all were in the unvaccinated group. So, we know that the vaccine works.

WHO’s recommendation

However, because of delays in availability of the second dose of the vaccine (and here the data included do not count the individuals who received a half dose of the vaccine), 59% of the people got their second dose between four and eight weeks after the first dose, 22% got the second dose between nine and 12 weeks, and 16% got it more than 12 weeks after the first dose. In these individuals, the vaccine efficacy was 56%, 70% and 78% respectively. The numbers are in the low thousands, but there is a clear trend of increasing efficacy with longer intervals between doses. In addition, when the immune response was measured, it was found that the longer the intervals between the two doses, the better was the immune response. These are the data based on which the WHO made the recommendation of an interval of eight to 12 weeks between two doses of the AstraZeneca vaccine.

What about use in older adults? Immunogenicity data from the AstraZeneca vaccine show that older individuals had an immune response comparable to other age groups. However, among the efficacy trial participants for whom data were available till December 7, 2020, only one in ten were older than 65 years. Among them, there were only 12 cases of symptomatic infection — four among the vaccinated and eight in the unvaccinated, which is a vaccine efficacy of 52%, but with a large range. Of the 12 cases, two needed hospitalisation, and both were unvaccinated. However, again, the numbers are too small for firm conclusions. Based on these data, first Germany, and then other European countries decided not to use the vaccine for older individuals.

But these countries also have supplies of the Pfizer-BioNTech mRNA vaccine, for which data on a larger number of older individuals are available. Thus, the countries can prioritise that vaccine to protect their elderly. More data from ongoing efficacy vaccine studies will become available to allow for a change of recommendations, if needed, in countries that have decided not to use the vaccine. But the WHO has taken both immunogenicity and available efficacy data into account and recommended the use of vaccines for older individuals.

Why have French experts recommended a single dose for those who have been previously infected with SARS-CoV-2? There are data from people who have been infected before which show that they make more antibodies with the first dose of vaccine (known as boosting), but not with the second dose. Based on this, immunologists think that an infection and one vaccination dose are together equivalent to two doses of the vaccine and will give equal or better protection.

While this is a rational and evidence-based approach, there are nuanced aspects that need to be addressed. Is vaccination required at all for people who have been infected? We have data to show that natural infection provides 83% protection for at least five months, and the WHO guidance states that individuals who have been infected can wait six months before getting vaccinated. This is an area that needs research to determine the level and duration of protection from infection, or infection and vaccination. If we had a way of measuring who was protected and who was not without waiting for them to be exposed to the virus and get sick, then answering these questions would be easier. But there is no such correlate of protection as yet.

The way forward

What should India do? We need to build platforms to study vaccine performance and not just rely on data that emerges from other countries. The number of vaccines is going to increase, and comparisons will become more important to gain clarity about which vaccines can be used for whom and how.

We have global data at this time that support a longer interval (at least for the Covishield vaccine) to improve efficacy, and we also have the current luxury of a declining trend in cases, which makes it easier for us to consider the longer-interval idea. This also brings the additional benefit of reaching more people in India with the first dose, while we wait for supplies with the ramping up of manufacturing of vaccines in India. There is another benefit of sharing vaccines with the world — the more we distribute vaccines to the rest of the world, the greater the chance that we decrease the import of variant viruses to India.

Gagandeep Kang is a Professor at Christian Medical College, Vellore

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