A team of scientists from Estonia has recently characterized the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response induced by an mRNA-based coronavirus disease 2019 (COVID-19) vaccine in relation to age, sex, and side-effects.

The findings reveal that although the two-dose vaccine regimen initially induces robust antibody response in all age groups, older male individuals are particularly associated with a gradual decline in vaccine-induced immunity six weeks after the second vaccine dose. The study is currently available on the medRxiv* preprint server.

Background

After successful development and clinical validation, several COVID-19 vaccines are currently rolling out worldwide to curb the uprising trajectory of the pandemic. Among all vaccine types, so far, mRNA-based vaccines have shown the highest efficacy in preventing SARS-CoV-2 infection and reducing mortality. For instance, in the phase 3 clinical trial, the two-dose regimen of Pfizer-BioNTech mRNA vaccine (BNT162b2) has shown an acceptable safety level and 95% efficacy against COVID-19.

However, studies investigating the impacts of age, sex, ethnicity, and other demographic factors on vaccine efficacy have shown that older individuals are particularly more likely to exhibit a weaker immunity in response to COVID-19 vaccination.

In the current study, the scientists have explored the dynamics of IgG-specific anti-SARS-CoV-2 antibody response after the first and second doses of Pfizer-BioNTech mRNA-based COVID-19 vaccine BNT162b2. They have also investigated whether age, sex, and vaccine-related side-effects can influence the vaccine efficacy.

Study design

The study was conducted on 118 healthy volunteers (age range: 21 – 68 years) who received two doses of the BNT162b2 vaccine. The immune responses of the volunteers were examined up to 6 weeks following the second vaccine dose. Specifically, the post-vaccination time points for monitoring immune response were three weeks after the first dose, just before the second dose, one week after the second dose, and six weeks after the second dose. The post-vaccination immune responses were compared with the baseline immune response (before the first vaccine dose).    

The serum samples collected from the volunteers were analyzed for IgG-specific antibodies against the spike receptor-binding domain (RBD) of SARS-CoV-2.

Important observations

By estimating serum antibody titers, the scientists observed that compared to the baseline values, the anti-spike RBD antibody levels increased three weeks after the first vaccine dose. The antibody levels peaked at one week after the second dose, followed by a gradual decline. Specifically, they observed a 45% reduction in antibody level between one and six weeks after the second dose. The majority of volunteers showed a similar trend of declining antibody levels. However, only 4% of volunteers exhibited increased antibody levels at six weeks after the second dose.

Interestingly, they observed that the IgG-specific anti-spike RBD antibody levels in COVID-19 recovered patients were significantly lower than observed in volunteers who received the second vaccine dose. However, volunteers immunized with only the first dose showed relatively lower antibody levels than COVID-19 recovered patients.

Factors influencing vaccine response

The scientists identified age as a major contributing factor for vaccine efficacy, which showed a negative correlation with antibody response at all time points tested. The volunteers aged less than 40 years showed significantly higher antibody levels at all tested time points compared to those above 40 years.

Furthermore, they observed that the negative correlation between age and vaccine-induced immune response was significantly more prominent in male volunteers than female volunteers.

Vaccine-related side-effects

About 93% of volunteers reported having mild to moderate side-effects, including swelling/pain at the injection site, fatigue, malaise, headache, chills, fever, or myalgia. However, about 22% of volunteers reported having long-lasting side-effects that resulted in workplace absenteeism and impaired daily life activities.

Interestingly, some of the side-effects, including fever, headache, fatigue, malaise, chills, and nausea, showed a strong positive correlation with vaccine-related immune responses. This correlation was significantly more prominent among male volunteers than female volunteers. Regarding age variation, older volunteers showed relatively fewer adverse side-effects than younger volunteers.

Study significance

The study findings reveal a robust antibody response among healthy volunteers immunized with Pfizer/BioNTech mRNA-based COVID-19 vaccine. This observation further strengthens the effectiveness of mRNA-based vaccines in controlling the COVID-19 pandemic.

Furthermore, the study indicates that the vaccine is relatively less effective in older males than older females. However, older people are less susceptible to have vaccine-related side-effects than younger people.

*Important Notice

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.

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.