Pfizer has submitted to the FDA Phase 2/3 trial data of mRNA vaccine on children 5–11 years for initial review. A formal submission to request for emergency use authorisation is expected in the coming weeks.
On September 20, Pfizer released details of the trial that showed the vaccine was safe and generated a “robust” antibody response in young children. Going by past experience, the FDA might greenlight the vaccine for young children in a matter of weeks. The company expects to submit data of children 2–4 years and 6 months to 1 year by the end of the year.
In an email, Dr. Gagandeep Kang, Professor of Microbiology at CMC Vellore, and Dr. Chandrakant Lahariya, physician-epidemiologist, discuss whether young children should be vaccinated and if that would further exacerbate vaccine inequity globally.
Considering that children below 11 years rarely suffer from severe disease and death, is it necessary to vaccinate young children?
Gagandeep Kang: All decisions about children needing to be vaccinated are based on assessment of risk and benefit. Here, when making decisions for public health, we also need to separate the benefits of vaccination against disease and against infection. If the risk from disease is low, then the risks of side-effects of vaccination need to be evaluated against the potential benefits of preventing a few cases. When we come to protection afforded by vaccines against infection, we need to understand whether infected children are a source of infection for the community. If children transmit infections, without themselves having severe disease, there may still be a benefit in vaccination. However, decisions need to be based on evidence, and as with other infectious diseases, transmission by children may be dependent on the amount of virus circulating in the community as well as the prior exposure of the community, and this will vary by geography.
Chandrakant Lahariya: Conducting clinical trials of COVID-19 vaccines in all age groups that are affected by the pathogen/disease is a standard process. However, the licensing and availability of an effective vaccine does not mean we need to find an arm to administer it. At present, there is not enough evidence to prioritise all children in 12–17 years over the vaccination of adults.
Is it safe to vaccinate young children considering the small risk of myocarditis (inflammation of heart muscle) and pericarditis (inflammation of the outer lining of the heart) seen in adolescents and young adults after the second dose of the mRNA vaccine?
Gagandeep Kang: Myocarditis and pericarditis have been reported after the mRNA vaccines, particularly in young males. These are not common side-effects, and as with every other vaccine, we need to balance the small risk and the potential benefit.
The data provided by Pfizer are likely to be sufficient for approval. It is for public health authorities to decide whether they want to introduce vaccination into national immunisation programmes. Even if public health authorities in a country decide not to introduce the vaccine, it is possible that parents may decide, with the advice of their doctors, that they want to achieve protection for their children. In that case, would we want to override the decisions of parents for their children?
Is the trial carried out on just 2,268 participants aged 5–11 years sufficient to understand the safety profile of the vaccine?
Gagandeep Kang: Yes, that is sufficient information for approval. Usually, safety assessments are carried out in a few thousand individuals across a much wider age range. We already have data for older children and adults. The vaccines are generally safe as no strong signals have been detected in the trials. The small risk of viral myocarditis was identified in adults and adolescents after the mRNA vaccine was widely used, indicating that in the countries that are reporting the data, there is effective monitoring of adverse events following immunisation. Understanding the level of risk is important for all decisions regarding introduction and continued use of vaccines. If decisions are made to introduce vaccines in young children, post-introduction monitoring for safety will need to continue as for all other vaccines.
Chandrakant Lahariya: The information on the safety of vaccines is generated from the data of all trial participants. The subgroup provides an indication on safety profile. However, more than safety, the smaller trials in children examine immunogenicity (whether vaccines are generating immune response); dose response (what dose of vaccine generates comparable immune response) and reactogenicity to various doses. What we need to remember is that trials are designed to identify common adverse events. However, rare adverse events which happen at a frequency lower than one in trial size can only be identified after roll-out of vaccines. That’s why the post-marketing surveillance (after vaccine roll-out) and stronger AEFI reporting systems are very relevant.
Unlike 30 microgram dosage given to adults, is reducing the dosage of vaccines to 10 microgram in children 5–11 years likely to make the vaccine safer?
Gagandeep Kang: When there is a side-effect of a vaccine, it does not always depend on the amount of active ingredients in the vaccine. It could also depend just on the presence or absence of one of the ingredients and how the vaccinated person responds to it. If there was a dose response, as in a higher dose carries a higher risk, then it is possible that there would be a lower risk in young children or with a lower dose. However, we do not know that at this time.
Chandrakant Lahariya: The rare systemic adverse events, such as viral myocarditis, are not dose-dependent. The purpose of reduced dose is to achieve a similar level of immune response and reduce or minimise local reactions, which sometimes are reported at higher frequency in children. Moreover, if the same immune response can be achieved with a lower dose of the vaccine, more children can be vaccinated.
Director of National Institute of Allergy and Infectious Diseases (NIAID) Dr. Anthony Fauci was quoted as saying that he expects approval from the U.S. Food and Drug Administration (FDA) in a few weeks and vaccination of young children might begin by the end of October. After booster shots for certain categories of adults, does vaccination of young children further impact the supply of precious vaccines to low- and middle-income countries and thus further exacerbate vaccine inequity?
Gagandeep Kang: Yes, vaccinating children at a time when vulnerable people in other parts of the world have not been vaccinated is a problem for global vaccine equity. However, all countries make their decisions for the benefit of their citizens first, and then think about the rest of the world.
Chandrakant Lahariya: Every country is free to determine what criteria it wishes to adopt to vaccinate different sets of population groups. The vaccination decisions are based upon the burden of disease, safety and efficacy of vaccines and availability of supply. All of these are considered together.
If a country gives importance to availability of supply of vaccines to administer to additional population groups, it has the right to do so, but then, in doing so, it fails in ethical and moral principles of vaccination drives.
According to a survey published last month, only 26% of parents of young children are ready to immediately vaccinate their children, while 40% wish to wait and watch and 25% don’t want to vaccinate. Is the reluctance to vaccinate young children peculiar to this vaccine or do we see it whenever a new vaccine is introduced?
Gagandeep Kang: All parents want to ensure that they do their best for their children. When a disease is severe and the risk of infection is high, and a vaccine is likely to protect, then it is more likely that parents will want to vaccinate their children. When data on vaccine safety are limited, or disease is not severe in children and the risk of infection is low, parents are less likely to vaccinate their children. This cannot be considered peculiar to any particular vaccine.
