Serological responses to heterologous COVID-19 mRNA vaccination in older individuals

The accelerated development of several vaccines has helped in the fight against the coronavirus disease 2019 (COVID-19).

Study: Real-world serological responses to extended-interval and heterologous COVID-19 mRNA vaccination in frail, older people (UNCoVER): an interim report from a prospective observational cohort study. Image Credit: Tirachard Kumtanom / Shutterstock.com

Background

Messenger ribonucleic acid (mRNA)-based vaccines including the Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2 vaccines, for example, have demonstrated a significant serological response.

However, the global scarcity of these vaccines has led to the deferring of the booster doses to ensure that as many high-risk individuals as possible could receive the first dose of these vaccines. This has subsequently delayed the administration of the second and booster doses of these vaccines.

In addition to vaccine supply concerns, the potential of immunosenescence, which can lead to a reduced immunological capacity to respond to both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and COVID-19 vaccines, can also increase the risk of high-risk individuals acquiring severe SARS-CoV-2 infections.

In Québec, Canada, a 16-week interval between the first and second vaccine doses was implemented for older individuals in long-term care. Although this policy helped in administering the first vaccine dose in high-risk populations, their antigenicity beyond the first dose was unknown in older individuals.

A new UNderstanding CoV-2 Vaccination in Elderly Residents (UNCoVER) study published in The Lancet Health Longevity aimed to assess the serological response to a real-world COVID-19 vaccination strategy in older individuals who resided in long-term care facilities.

About the study

The current study included participants who resided in long-term care facilities was conducted from December 31, 2020, to June 9, 2021. Clinical data that included the patients’ medical history, previous SARS-CoV-2 infection, and vaccination status were collected from each participant. The frailty status was assessed with the help of the Clinical Frailty Scale.

Blood samples were collected from the participants at different time points, including before administration of the vaccine (t1), four weeks after receiving the first dose vaccine dose, which coincided with the timing of the second dose as done in clinical trials (t2), six to ten weeks after the first dose (t3), up to two days before the administration of the second dose (t4), and at four weeks post the second dose (t5).

Study participants were divided into two cohorts. In the first cohort, which was referred to as the discovery cohort, blood samples were collected from the t1 time point. Comparatively, in the second cohort, referred to as the confirmatory cohort, blood samples were collected from the t2 time point onwards.

Automated chemiluminescent enzyme-linked immunosorbent assay (ELISA) was used for the detection of immunoglobulin G (IgG) antibodies to the SARS-CoV-2 trimeric spike protein, nucleocapsid, and receptor-binding domain (RBD) of the spike protein to distinguish between natural infection and vaccine-induced immunity.

Study findings

Out of the 185 participants included in the study, the majority were White females with a median age of 83 years. A total of 181 of the 185 individuals included in this study had at least one coexisting condition, all of whom had an average frailty score of 6.57.

For 149 participants, their first vaccine dose was the mRNA-1273 vaccine, whereas the remaining 36 participants received the Pfizer-BioNTech BNT162b2 vaccine. Comparatively, 65 individuals received a second dose with the mRNA-1273 vaccine, whereas 120 individuals received the BNT162b2 vaccine for their second dose. Taken together, 65 participants received two doses of mRNA-1273, 36 received two doses of BNT162b2, and 84 received mRNA-1273 followed by BNT162b2.

The discovery cohort consisted of a higher proportion of participants with previous SARS-CoV-2 infections, as well as a higher proportion to receive a heterologous prime-boost as compared to the confirmatory cohort. The median time between the first and second dose was 112 days for those who received two doses of mRNA-1273, 96 days for those who received two doses of BNT162b2, and 111 days for those who received mRNA-1273 followed by BNT162b2.

Previously infected participants maintained higher levels of anti-nucleocapsid reactivity for subsequent time points as compared to those who were not previously infected. However, a significant rise in anti-spike IgG concentrations was observed four weeks after the prime dose irrespective of infection status. Similar levels were also observed at t2 and t3 timepoints.

However, a reduction in mean anti-spike IgG responses was observed in uninfected individuals at t4 as compared to previously infected individuals. This difference in response was resolved by the t5 timepoint.

Anti-RBD IgG concentrations at t1 were higher in previously infected individuals. A decline in anti-RBD and anti-spike IgG concentrations was observed in the discovery cohort, regardless of infection status, which was followed by an increase four weeks later.

Previously infected individuals reported higher anti-RBD IgG activity from t2 to t4. However, anti-RBD IgG levels were comparable at t5.

Individuals who received two doses of BNT162b2 exhibited a reduction in anti-RBD IgG antibodies from t2 to t4, irrespective of previous infection status. Individuals who received two doses of mRNA-1273 with previous SARS-CoV-2 infection showed no significant change in antibody response, while uninfected individuals exhibited a decrease in anti-RBD IgG antibodies.

However, at t5, an increase in antibody concentrations was observed in all groups. No decrease in antibody responses was observed with an increase in age.

Conclusions

Taken together, the current study demonstrates that no difference in antibody responses was associated with an increase in age. The study findings also indicated that mRNA-based vaccines could be used with a maximum interval of 16 weeks between the doses.

The continued emergence of SARS-CoV-2 variants, along with the global shortage of vaccines, requires the development of rationing policies in different regions. Further research needs to be carried out to determine the role of extended-interval vaccination in protection against new SARS-CoV-2 variants.

Limitations

The study had certain limitations, including the small sample size, the majority of whom were White. An additional limitation was that no data on vaccine effectiveness against infection or disease, as well as any information on cellular responses, was available during the study period.

Written by

Suchandrima Bhowmik

Suchandrima has a Bachelor of Science (B.Sc.) degree in Microbiology and a Master of Science (M.Sc.) degree in Microbiology from the University of Calcutta, India. The study of health and diseases was always very important to her. In addition to Microbiology, she also gained extensive knowledge in Biochemistry, Immunology, Medical Microbiology, Metabolism, and Biotechnology as part of her master's degree.