Delaying Second Dose of Pfizer COVID-19 Vaccine Increases Antibody Response in the Elderly

A new pre-print study suggests that extending the dose interval of the second Pfizer–BioNTech COVID-19 vaccine (BNT162b2) by twelve weeks significantly increases the immune response in individuals aged 80 or over.

An emergency situation

The Pfizer–BioNTech COVID-19 vaccine is an mRNA-based vaccine that received emergency use authorization in the UK in December 2020. In January 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) announced that it would be changing the vaccine dosing schedule in the UK by extending the period of time between the first and second dose to a maximum of 12 weeks. This change was deemed necessary due to the worsening situation in the UK, as confirmed COVID-19 cases and fatalities began to climb. By changing the regimen, the MHRA hoped to increase the speed of the vaccine rollout program.

The clinical trials that tested the currently authorized COVID-19 did not adopt this regimen; they tested the safety and the efficacy of the vaccines using an interval period of three weeks between the first and second dose.

Now, a research study funded by the UK Research and Innovation (UKRI) and the National Institute for Health Research (NIHR) has explored the immunogenicity of this extended vaccination period, focusing on the BNT162b2 vaccine. First author Dr Helen Parry, NIHR academic clinical lecturer at the University of Birmingham, explained why this research is important for elderly people: "It is known that immunity reduces with aging and responses to vaccination also decline with age. People of older age are also more susceptible to severe COVID-19. Therefore, it is crucial that we study the immune response to COVID-19 vaccines in this vulnerable cohort," she said.

The study recruited a sample of 172 individuals aged 80 years and above. Ninety nine participants were allocated to receive the BNT162b2 vaccine at the standard 3-week interval between doses (median age 84 years), and 73 participants received their second vaccine 11-12 weeks after the first dose (median age 84 years). The researchers compared the spike-specific antibodies and cellular immune responses across the groups. It is important to measure both antibody and cellular responses to the vaccine as they represent two different arms of the adaptive immune response.

Antibody response measurements were performed by Public Health England (PHE), whereas the cellular response measurements were performed at Oxford Immunotec. "The technique involves stimulating blood cells overnight with Spike specific peptides and then looking to see how much IFN-gamma is released by the T cells," explained Parry.

Extended interval, higher antibody response

The researchers found that the peak antibody responses were 3.5 times higher in the extended interval group, compared to those who received their second vaccine dose after 3 weeks. "The peak cellular response was higher in those who received the vaccine 3 weeks apart, although by 14 weeks, both groups showed similar frequencies of response," Parry told Technology Networks.

Dr Gayatri Amirthalingam, consultant epidemiologist at PHE, said: “The higher antibody responses in people receiving two doses of the Pfizer vaccine using an extended 12-week interval provides further supportive evidence of the benefits of the UK approach to prioritise the first dose of vaccine."

“Our research findings may be important in the development of global vaccination strategy as extension of interval of the second vaccine dose in older people may potentially reduce the need for subsequent booster vaccines," Professor Paul Moss, corresponding author, said. 

The study authors highlight that the elderly participants used in the study is one limitation. "It is not clear how translatable the findings are to younger people," said Parry. Currently, the researchers do not have any plans to expand their work to other age groups. "We are aware that younger health care workers are being studied and the CONSENSUS study by PHE should also have results for different age demographics with time," Parry concluded.

Helen Parry was speaking to Molly Campbell, Science Writer for Technology Networks.  

Reference: Parry H, Bruton R, Stephens C et al. Extended interval BNT162b2 vaccination enhances peak antibody generation in older people. medRxiv. 2021. doi: 10.1101/2021.05.15.21257017.