In the absence of therapeutic intervention, vaccines are the only available avenue to contain the COVID-19 (coronavirus disease 2019) pandemic. Currently, vaccines against the causal agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are being administered globally.
It is essential to understand the vaccine response to know its efficacy under diverse plans and cohorts. The duration of protection imparted by the current vaccine is unknown in a real-world setting. This is important, particularly in underrepresented groups in clinical trials. One such group is the elderly population, aged above 80 years, who are at the most significant risk of death from COVID-19 disease.
To date, clinical trials have not provided much information on the vaccine efficacy or the neutralizing responses in individuals above the age of 80. To throw light on these aspects, researchers undertook a post-vaccination immunogenicity study in the elderly population.
In a recent medRxiv* preprint publication, the team led by Professor Ravindra K. Gupta has assessed the real-world immune responses following the vaccination against the SARS-CoV-2. The team measured 1) IFN-gamma (interferon-gamma) T cell responses, 2) both total IgG Spike/ IgG Spike RBD (receptor binding domain) and 3) neutralizing antibody responses to Spike in sera.
The spike (S) protein is present on the virus's surface; via this protein, the virus enters the host human cell. The vaccines developed to target this region of the protein, and the antibodies are developed against it.
The mRNA-based vaccine BNT162b2 was administered to populations in the UK on a two-dose approach, separated by a three-week gap. In this study, the cohort included 26 participants. The median age was 82 years.
After each dose of the vaccines, the team analyzed the T cell responses and the antibody activity. They observed that the T cell responses did not correlate with serum neutralization after the first dose.
As expected, the neutralization activity increased between the first and second doses. Notably, they observed poor neutralization activity only in the elderly population - over 80 (compared to those under 80) after the first dose.
When tested three weeks after the second dose, they found increased neutralizing titers between the first and second doses. They observed no significant difference between participants above and below the age of 80 after the second dose.
The researchers also used an approved rapid finger prick antibody test detecting S antibodies to test the participants at both time points. They observed a positive neutralization with 42% sensitivity and 100% specificity three weeks after the first dose. Three weeks after the second dose, it was with 95% sensitivity and 100% specificity.
These rapid antibody testing help to identify suboptimal responders following the second dose and, with evaluation, determine the requirement of boosting.
Here, the researchers describe the immunogenicity data from the real world roll out after the first dose of Pfizer BNT162b2 vaccine, focusing on responses in individuals around age 80. This study shows that among the individuals above the age of 80, certain individuals exhibit suboptimal neutralizing antibody response three weeks after vaccination, whereas the second dose is associated with robust neutralizing responses.
“It will be important to follow all participants over the following months to measure the kinetics of neutralization activity as well as data on reinfection”
Importantly, individuals over 80 years old are likely to be at prolonged increased risk for infection until the second dose. Thus, the SARS-CoV-2 infection during an enlarged window period between doses in the presence of only partially protective antibody titers could generate conditions for selecting escape mutations, the researchers write.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Age-related heterogeneity in Neutralising antibody responses to SARS-CoV-2 following BNT162b2 vaccination, Dami Collier, Isabella Ferreira, Rawlings Datir, Bo Meng, Laura Bergamaschi, The CITIID-NIHR Bioresource COVID-19 Collaboration, Anne Elmer, Nathalie Kingston, Barbara Graves, Barbara Graves, Kenneth GC Smith, John Bradley, Paul Lyons, Lourdes Ceron-Gutierrez, Gabriela Barcenas-Morales, Rainer Doffinger, Mark Wills, Ravindra K Gupta, medRxiv. 2021.02.03.21251054; doi: https://doi.org/10.1101/2021.02.03.21251054, https://www.medrxiv.org/content/10.1101/2021.02.03.21251054v1