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 Third COVID-19 vaccine doses are broadly recommended, but immunogenicity data remain limited, particularly in older adults. Methods We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain, ACE2 displacement, and virus neutralization against ancestral and Omicron (BA.1) strains from pre-vaccine up to one month following the third dose, in 151 adults aged 24-98 years who received COVID-19 mRNA vaccines. Results Following two vaccine doses, humoral immunity was weaker, less functional and less durable in older adults, where a higher number of chronic health conditions was a key correlate of weaker responses and poorer durability. One month after the third dose, antibody concentrations and function exceeded post-second-dose levels, and responses in older adults were comparable in magnitude to those in younger adults at this time. Humoral responses against Omicron were universally weaker than against the ancestral strain after both the second and third doses. Nevertheless, after three doses, anti-Omicron responses in older adults reached equivalence to those in younger adults. One month after three vaccine doses, the number of chronic health conditions, but not age, was the strongest consistent correlate of weaker humoral responses. Conclusion Results underscore the immune benefits of third COVID-19 vaccine doses, particularly in older adults.

Serial infection with SARS-CoV-2 Omicron BA.1 and BA.2 following three-dose COVID-19 vaccination

“…The authors concluded that such events were rare (<0.1% of cases during the brief window of analysis) and more likely to occur among unvaccinated individuals, but further evaluation of the data indicates a majority of reinfection cases were due to BA.2 following BA.1. Moreover, given that the present case participant was one of only 151 enrolees of an observational COVID-19 vaccine study (25,26), our results suggest that the risk of serial infection with Omicron subvariants may be greater than current assumptions based on low reinfection rates. We note however that the participant's status as a frontline healthcare worker may have resulted in an increased risk of exposure and (re-)infection over the general population.…”

“…The observation that average humoral responses to three-dose vaccination failed to protect against Omicron BA.1 infection is consistent with the extremely high rates of community transmission observed in many regions during the recent Omicron-driven pandemic waves. Given that third doses substantially boost humoral responses in individuals of all ages (29)(30)(31)(32), the risk of Omicron infection is likely to be higher among individuals who have received fewer than three doses (18,33) and is likely to increase with time following vaccination due to natural declines in antibody responses (26,(34)(35)(36)(37). Additional studies are needed to assess these factors.…”

“…In December 2020, we established a prospective longitudinal study in Vancouver, Canada, to examine SARS-CoV-2 specific humoral immune responses following vaccination with BNT162b2 (Comirnaty; BioNTech/Pfizer) or mRNA-1273 (Spikevax; Moderna) in a cohort of 151 adults aged 24-98 years (described in (25, 26)). Serum and plasma were collected longitudinally up to 6 months following the third dose (Figure 1A).…”

Retrospective Cohort Study of the Effectiveness of the Sputnik V and EpiVacCorona Vaccines against the SARS-CoV-2 Delta Variant in Moscow (June–July 2021)

“…Our retrospective cohort analysis revealed a consistent decline in the estimated vaccine effectiveness with age. Although we attribute this decline to the assumption that there are more people with comorbidities among the elderly vaccinated compared to the unvaccinated of the same age, we do not rule out that in the elderly, vaccine-induced protective immunity can weaken more quickly because their antibody levels might decrease faster, as shown in a number of publications for different vaccines [ 43 , 44 , 45 , 46 ]. After vaccination with BNT162b2, the level of antiviral IgG antibodies decreased faster in older vaccine recipients (≥50).…”

The effects of vaccination on the disease severity and factors for viral clearance and hospitalization in Omicron-infected patients :A retrospective observational cohort study from recent regional outbreaks in China

“…26 They may benefit enormously from active vaccination, 27 which can stimulate the production of neutralizing antibodies and promote viral clearance. Recent evidence demonstrates the safety and good tolerance of vaccines in the elderly with primary conditions 28 and a necessity of vaccinating the elderly 29 . In addition, the overall NAN median time of 15 days suggests that it is necessary to quarantine the infected people for at least 15 days in order to minimize the possibility of transmission, which may be prolonged for elderly people with primary conditions.…”