Older adults mount less durable humoral responses to two doses of COVID-19 mRNA vaccine, but strong initial responses to a third dose

Abstract

Background. Two-dose mRNA vaccines reduce COVID-19 related hospitalization and mortality, but immune protection declines over time. As such, third vaccine doses are now recommended, particularly for older adults. We examined immune response durability up to 6 months after two vaccine doses, and immunogenicity after a third vaccine dose, in 151 adults ranging in age from 24 to 98 years. Methods. Specimens were collected from 81 healthcare workers (median age 41 years), 56 older adults (median 78 years) and 14 COVID-19 convalescent individuals (median 48 years), at one, three and six months following the second dose, and from 15 HCW, 28 older adults and 3 convalescent individuals at one month following a third dose. Binding antibodies to the SARS-CoV-2 spike receptor binding domain were quantified using a commercial immunoassay. Virus neutralizing activity was assessed using a live SARS-CoV-2 infection assay. Results. Compared to healthcare workers, older adults displayed ~0.3 log10 lower peak binding antibodies one month after the second dose (p<0.0001) and modestly faster rates of antibody decline thereafter (p=0.0067). A higher burden 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 4-fold lower in older adults one month after the second dose (p<0.0001) and became undetectable in the majority of individuals by six months. One month after a third dose, binding antibodies and neutralizing activities surpassed peak values achieved after two doses in both healthcare workers and older adults, and differences between these groups were no longer statistically significant. Compared to both naive groups, convalescent individuals displayed slower rates of binding antibody decline (p<0.006) and maintained higher neutralizing activity six months after the second dose. Conclusions. Immune responses to two-dose COVID-19 mRNA vaccines are overall weaker in older adults, and also decline more quickly over time, compared to younger adults. A third COVID-19 mRNA vaccine dose enhanced binding and neutralizing antibodies to levels higher than those observed after two vaccine doses, but the rate of decline of these responses should be monitored, particularly in older adults with a higher burden of chronic health conditions.

Immunogenicity and safety after the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors on active treatment: a prospective cohort study

“…No differences were reported when the type of anticancer treatment (chemotherapy or immunotherapy) was correlated with the SARS-CoV-2 humoral response, while the age inversely correlated with total IgG level and NT Abs titre at baseline (T0) but not after the booster (T1). This finding confirms that the age is an unfavourable prognostic factor for long lasting humoral response after the two-doses of SARS-CoV-2 vaccine, but the booster is immunogenic also in older subjects, as highlighted by Mwimanzi and colleagues too [24]. Furthermore, we have also investigated the development of Spike-specific cell-mediated immune J o u r n a l P r e -p r o o f response using the SARS-CoV-2 Interferon Gamma Release Assay (IGRA) in a sample of subjects.…”

Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults

“…In the older adult cohort, receipt of a third vaccine dose largely eliminated disparities caused by sex, age, and frailty in antibody responses, with the exception of ACE2iAb, which remained lower in frail compared to non-frail or pre-frail participants. The effect of age on SARS-CoV-2 vaccine responses has been studied [7-9, 29-33], but the sex differential impact of age has not been reported previously. Furthermore, studies investigating frailty have not found an effect on antibody responses [34-36], but have reported that frailty increases the risk of post-vaccination breakthrough infection [37, 38], suggesting that the immunogenicity studies may have been under-powered to observe an effect of frailty or that lack of consideration of biological sex obscured the effect.…”

“…In the older adult cohort, receipt of a third vaccine dose largely eliminated disparities caused by sex, age, and frailty in antibody responses, with the exception of ACE2iAb, which remained lower in frail compared to non-frail or pre-frail participants. The effect of age on SARS-CoV-2 vaccine responses has been studied [7][8][9][29][30][31][32][33], but the sex differential impact of age has not been reported previously.…”

Efficacy, immunogenicity and safety of COVID-19 vaccines in older adults: a systematic review and meta-analysis

“…Since its initial discovery, the more transmissible and insidious Omicron has rapidly become the predominant variant prevalent worldwide, intensely threatening the neutralizing efficacy of current COVID-19 vaccines ( 100 , 101 ). The vulnerable population, particularly those unvaccinated or with coexisting underlying diseases, represents an unprecedented challenge in addressing Omicron spread ( 102 ). Several studies have confirmed that COVID-19 vaccines remain an effective protective measure in interrupting Omicron transmission; simultaneously, the mRNA vaccines, notably homologous or heterologous boosters, are worthy candidates for priority consideration ( 42 , 100 , 102 – 106 ).…”

“…The vulnerable population, particularly those unvaccinated or with coexisting underlying diseases, represents an unprecedented challenge in addressing Omicron spread ( 102 ). Several studies have confirmed that COVID-19 vaccines remain an effective protective measure in interrupting Omicron transmission; simultaneously, the mRNA vaccines, notably homologous or heterologous boosters, are worthy candidates for priority consideration ( 42 , 100 , 102 – 106 ). There was limited or no data on VE against various variants, including Omicron, in the elderly population.…”