Booster mRNA vaccination effective in reviving anti-SARS-CoV-2 antibody titers among the elderly

Vaccination camps started rolling out in December 2020, wherein people were advised two shots of mRNA vaccines, with time intervals of 4-8 weeks between two doses. Early-stage clinical trials and real-life evidence showed the vaccines to be effective in reducing severe disease, hospitalization and coronavirus disease 2019 (COVID-19) related death. However, one concern remains – that of waning immune protection over time.

Previous studies have shown that antibody titers confer protection for about 6 months before waning off gradually. This is even lower for the elderly, especially those with already low antibody titers, as shown through immunological assays. With new and highly transmissible variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) like the Omicron (B.1.1.529) variant, it is of paramount importance to have anti-spike antibody levels revived in the body for an effective response to infection.

Medical bodies have now advised people to take up a third vaccine dose or a “booster shot” to ramp up antibody levels, especially in older adults. With this regard, researchers published a study in the preprint server medRxiv* wherein they evaluated the durability of immune responses pot the initial double dose regimen of mRNA vaccines and the effect of a booster shot among the elderly.

Study details

Researchers collected sociodemographic data (age, sex, ethnicity), information on chronic health conditions and COVID-19 vaccination information through self-reports from patients and through medical records where available. Chronic health conditions were defined as high blood pressure, diabetes, asthma, obesity (BMI ≥30), chronic lung disease, liver, kidney, cardiovascular or hematological complications, cancer, and immunosuppression due to medication for chronic conditions, to generate a total score ranging from 0-11 per participant.

Researchers collected specimens from a total of 151 subjects with predominantly female participants. All participants received two doses of a COVID-19 mRNA vaccine between December 2020 and July 2021, with a maximum interval of 112 days in between doses.

The first lot had 81 healthcare workers (HCW) (median age 41 years), 56 older adults (median 78 years) and 14 COVID-19 convalescent individuals (median 48 years), whose samples were collected at an interval of one, three and six months following the second dose of an mRNA vaccine. Further, researchers collected samples from a second lot of 15 HCW, 28 older adults, and three convalescent individuals at one month following a third booster dose.

Binding antibodies to the SARS-CoV-2 spike receptor binding domain were quantified using a commercial immunoassay. The neutralizing capacity of antibodies was assessed using a live SARS-CoV-2 infection assay.

In comparison to the healthcare workers, older adults displayed ~0.3 log10 lower peak binding antibodies one month after the second dose (p<0.0001) and modestly significant faster rates of antibody decline thereafter (p=0.0067). The presence of severe cases of chronic health conditions was independently associated with faster rates of antibody decline after correction for age, sociodemographic factors, and vaccine-related variables. Peak neutralizing activity was significantly (4-fold) lower among the elderly, one month after the second dose (p<0.0001). By the end of the sixth month, the antibody levels were almost undetectable.

However, the booster dose was effective in reviving the levels of antibodies in the blood in all groups. One month after the booster dose, researchers found binding antibodies and neutralizing activities to have surpassed peak values, in both healthcare workers and older adults. Moreover, the differences between these groups were no longer statistically significant. Compared to both infection-naive groups, convalescent individuals displayed slower rates of binding antibody decline (p<0.006) and maintained higher neutralizing activity, even six months after the second dose.

Implications

Though immune responses to double-dose COVID-19 mRNA vaccines were overall weaker in older adults, and declined at a higher pace over time, compared to younger adults, a booster dose was effective in reviving the said antibody levels.

A booster dose was successful in taking binding and neutralizing antibodies to levels higher than those observed after the initial double-dose regimen. However, it would be impactful to know the longevity of these antibodies in the future and this data would be useful in planning the future course of action for booster doses among different populations, especially the elderly with a higher burden of chronic health conditions.

*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

Sreetama Dutt

Sreetama Dutt has completed her B.Tech. in Biotechnology from SRM University in Chennai, India and holds an M.Sc. in Medical Microbiology from the University of Manchester, UK. Initially decided upon building her career in laboratory-based research, medical writing and communications happened to catch her when she least expected it. Of course, nothing is a coincidence.