Geneva: With a number of countries facing exceptional circumstances of vaccine supply constraints combined with a high disease burden, World Health Organisation’s Strategic Advisory Group of Experts on Immunization (SAGE) has said these countries can consider delaying the administration of the second dose of the mRNA vaccine BNT162b2 developed by BioNTech and Pfizer, which has been shown to have an efficacy of approximately 95%, to allow for a higher initial coverage.
The data reviewed by WHO at this time support the conclusion that the known and potential benefits of BNT162b2 outweigh the known and potential risks.
On December 31, 2020, WHO listed the COVID-19 mRNA vaccine BNT162b2 for emergency use, making the Pfizer–BioNTech vaccine the first to receive emergency validation from WHO since the outbreak began a year earlier. The WHO Emergency Use Listing Procedure (EUL) is a risk-based procedure for assessing and listing unlicensed vaccines, therapeutics and in vitro diagnostics with the ultimate aim of expediting the availability of these products to people affected by a public health emergency
In a statement today, the WHO said the decision to delay the second dose was based on the observation that efficacy had been shown to start from day 12 after the first dose and reached about 89% between days 14 and 21, at the time when the second dose was given.
WHO said no data on longer term efficacy for a single dose of the mRNA vaccine BNT162b2 currently exist, as the trial participants received 2 doses with an interval between doses in the trial ranging from 19 to 42 days.
“Of note, neutralising antibody responses are modest after the first dose and increase substantially after the second dose. Countries experiencing exceptional epidemiological circumstances may consider delaying for a short period the administration of the second dose as a pragmatic approach to maximizing the number of individuals benefiting from a first dose while vaccine supply continues to increase,” the WHO stated.
WHO’s recommendation at present is that the interval between doses may be extended up to 42 days (6 weeks), on the basis of currently available clinical trial data. Should additional data become available on longer intervals between doses, revision of this recommendation will be considered. Countries should ensure that any such programme adjustments to dose intervals do not affect the likelihood of receiving the second dose.
The recommended schedule is two doses (30 µg, 0.3 ml each) given intramuscularly into the deltoid muscle. An interval of 21–28 days between the doses is recommended. If the second dose is inadvertently administered less than 21 days after the first, the dose does not need to be repeated. If administration of the second dose is inadvertently delayed it should be given as soon as possible thereafter, according to the manufacturer’s instructions. It is currently recommended that individuals receive no more than two doses in total.
WHO further stated there was currently no evidence on the need for a booster dose or booster doses of the vaccine after the current two-dose vaccine series was complete. The need for and timing of booster doses will be evaluated as further data accumulate, it said. As on interchangeability with other vaccines, it stated there were no data available on the interchangeability of Pfizer vaccine with other mRNA vaccines or other COVID-19 vaccine platforms. It is currently recommended that the same product should be used for both doses. “If different COVID-19 vaccine products are inadvertently administered in the two doses, no additional doses of either vaccine are recommended at this time. Recommendations may be updated as further information becomes available on interchangeability,” it stated.
Moreover, there should be a minimum interval of 14 days between administration of this vaccine and any other vaccine against other conditions, until data on co-administration with other vaccines become available. Besides, it added, a history of severe allergic reaction (e.g. anaphylaxis) to any component of the vaccine is a contraindication to vaccination. In particular, BNT162b2 should not be administered to individuals with a known history of severe allergic reaction to polyethylene glycol (PEG) or related molecules as PEG is a component of the vaccine.
“Anaphylactic reactions after administration of BNT162b2 vaccine have been reported outside of clinical trials. A history of any immediate allergic reaction to any other vaccine or injectable therapy (i.e. intramuscular, intravenous, or subcutaneous vaccines or therapies) is considered as a precaution but not a contraindication to vaccination. For such persons, a risk assessment should be conducted to determine the type and severity of reaction and the reliability of the information. Such individuals may still receive vaccination, but they should be counselled about the risks of developing a severe allergic reaction and the risks should be weighed against the benefits of vaccination. Such persons should be observed for 30 minutes after vaccination in health care settings where anaphylaxis can be immediately treated,” the WHO recommended.
Data from the phase 3 trial indicate that the efficacy and safety of the BNT162b2 vaccine were comparable across all age groups (above the age of 16) and vaccination was recommended for older persons and for persons with comorbidities that have been identified as increasing the risk of severe COVID-19.
Populations for which limited or no data exist from phase 2/3 clinical trials
Persons above 85 years of age
Persons above the age of 85 years and very frail older persons were not included in the clinical trials. However, the safety and immunogenicity data obtained in a large subset of older people with and without comorbidities suggest that the benefits of vaccination outweigh the potential risks. Vaccination is recommended for older persons without an upper age limit.
Children and adolescents below the age of 16 years
There are currently no efficacy or safety data for children or adolescents below the age of 16 years. Until such data are available, individuals below 16 years of age should not be vaccinated.
Pregnant or lactating women
The available data on BNT162b2 vaccination of pregnant women were insufficient to assess vaccine efficacy or vaccine-associated risks in pregnancy. However, it should be noted that the BNT162b2 vaccine is not a live virus vaccine, the mRNA does not enter the nucleus of the cell and is degraded quickly. Developmental and reproductive toxicology (DART) studies in animals have not shown harmful effects in pregnancy.
Further studies are planned in pregnant women in the coming months, the WHO stated, and recommended not to use BNT162b2 in pregnancy, unless the benefit of vaccinating a pregnant woman outweighs the potential vaccine risks, such as in health workers at high risk of exposure and pregnant women with co-morbidities placing them in a high-risk group for severe COVID-19. WHO also did not recommend pregnancy testing prior to vaccination.
Moreover, there were no data on the safety of COVID-19 vaccines in lactating women or on the effects of mRNA vaccines on breastfed children. As the BNT162b2 vaccine is not a live virus vaccine and the mRNA does not enter the nucleus of the cell and is degraded quickly, it is biologically and clinically unlikely to pose a risk to the breastfeeding child. On the basis of these considerations, a lactating woman who is part of a group recommended for vaccination, e.g. health workers, should be offered vaccination on an equivalent basis. WHO does not recommend discontinuing breastfeeding after vaccination.
– global bihari bureau
