Cautious optimism from recent results of Covid-19 vaccines

Neelam Sen, JNU
 

With the increasing number of COVID-19 infections around the world, developing vaccines is critical for controlling the pandemic. Vaccines are substances that help prevent infections. Typically, they contain an agent that resembles the germ causing a disease, which activates the immune system to recognize and destroy the germs. COVID-19 vaccines are expected to provide immunity to large sections of  populations and thus alleviate the pandemic situation. Recently published results about the ChAdOx1 nCov-19 vaccine 1 (co-developed by Oxford University and AstraZeneca in the UK) and mRNA-1273 vaccine2 (co-developed by National Institute of Allergy and Infectious Diseases and Moderna in the US) from their first and second stage trials have provided hope to many countries around the world in the midst of the COVID-19 pandemic. 

 

The development of vaccines typically takes several years, involving initial exploratory research to formulate the vaccine, followed by pre-clinical testing with animals to test safety and effectiveness. This is followed by at least 3 stages of human clinical trials. The first and second stage human clinical trials of the vaccine try to answer the questions ‘Is it safe?’ and ‘Does it activate an immune response’, respectively. The critical third stage clinical trial asks how effectively the vaccine protects a population group against the disease. Regulatory approvals have been given in cases that have efficacies ranging from 50% (flu vaccines) to 98% (measles vaccines). 

 

Results from the early stage trials of the two COVID-19 vaccines mentioned above have shown that they are mostly safe and only show local or systemic reactions that are commonly associated with vaccinations, and that the overall efficacy of these two vaccines appear positive. However, it is important to note the constraints of drawing overly optimistic perceptions of the vaccines. For example, the stage 1 & 2 trials for ChAdOx1 nCov-19 vaccine was limited to 129 individuals in the UK (mostly white) and the 56-day study is less than 10% of the one year further follow up period that is intended [1]. The Moderna mRNA-1273 vaccine was tested on 45 healthy adults in the US of which 89% were white and observations were again limited to 56 days [2]. Both vaccines reported an increased immune response characterized by an increase in viral specific antibodies by day 28. Their data also show an understandably wide range of responses across individuals. In the limited statistical and biological understanding that these studies provide, it is clear that the vaccines have some success in activating the immune response but this response varied among those who were administered the dose. 

 

Critical Phase 3 trials will provide better insights into the effectiveness of these vaccines. It is particularly important to notice the range values of drug safety and efficacy especially as multiple ethnicities, age-groups and co-morbidities are taken into account. For example, the Drugs Controller General of India approved phase 2 & 3 trials of ChAdOx1 nCov-19 vaccine in India across 17 selected sites. These trials will provide a clearer understanding of how varied the response of the vaccine would be for different ethnic groups and common comorbidities prevalent in the Indian population. It is important to note that the speed at which these vaccines are being developed is unprecedented and any expectations from vaccines should only be based on available scientific data.

  [1] Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial, Lancet (2020)

[2] Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2 — preliminary report, New England Journal of Medicine (2020)

[Last updated 22 August 2020]