Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose

Abstract

The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2–related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.

Prevention of cyclical resurgences of COVID-19-like pandemics in the long term: What are the trade-offs?

“…To capture the stratified effect of disease burdens in detail, the model divided the initial total cases averted into five stratified health metrics including symptomatic, asymptomatic, hospitalized, ICU, and death cases averted, and the statistics of these measures were calculated respectively based on the statistics data in (7) and (8). Additionally, the model assumed: (a) the population was homogenous and identical population size of each age group; (b) individuals with at least one dose vaccinated were infected with no symptoms (i.e., asymptomatic) due to partial immunity protection of vaccines; (c) the relative infectiousness of other types of infections was identical to the primary infections; (d) the primary vaccination was initiated at week 44, nearly eleven months after the establishment of the transmission; (e) to reflect seasonal variation in transmission, the model based seasonal reproduction numbers in this work on those used in (5), which calibrated values to yield the basic reproduction number of 2.3;…”

“…Different countries enacted varied campaigns of vaccination in compliance with the objectives of health policies to balance the trade-offs between the health output of the populations and economic activities (2,3). Retrospectively, vaccines, transmission traits of the pathogen, and vaccination strategies had a combined impact on the risks of infections and subsequent health outcomes (5)(6)(7)(8)(9)(10). The data by WHO indicated that there were more than 100 vaccine candidates in clinical usage worldwide by 2023 (1)(2)(3)(4).…”

“…It was of difficulty to exactly capture each of the traits of alternative vaccines in model analyses (11)(12)(13)(14)(15). There were heterogeneities and uncertainties regarding the landscape of vaccination, immunity-strength and immunity-waning profiles of doses, and the social effort (1)(2)(3)(4)(5)(16)(17)(18)(19)(20). Is there a long-term difference in curbing infections and other disease burdens by enacting the booster vaccination versus a primary strategy conditional on the traits of vaccines?…”

Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology

“…Observational cohort studies of healthy adults ( 6 , 7 ) demonstrate that aging leads to baseline increases in plasma concentrations of pro-inflammatory cytokines ( 6 , 8 ), several of which, such as interleukin-6 (IL-6), are well-known biomarkers of COVID-19 severity, suggesting potential connections between the pathophysiology of human aging and COVID-19 ( 8 ). Juxtaposed against this state of aging-associated inflammation are functional impairments in innate and adaptive immune signaling observed during the vaccination of aged individuals ( 9 – 12 ). Furthermore, recent human in vitro data indicate that aging results in impaired production of type I interferons (IFNs) in monocytes and dendritic cells after Toll-like receptor (TLR) ligation, suggesting disrupted innate immunity ( 13 – 17 ).…”

Host-Microbe Multiomic Profiling Reveals Age-Dependent COVID-19 Immunopathology

“…Observational cohort studies of healthy adults 5,6 demonstrate that aging leads to baseline increases in plasma concentrations of proinflammatory cytokines 5,7 , several of which (e.g., IL6) are well-known biomarkers of COVID-19 severity, suggesting potential connections between the pathophysiology of human aging and COVID-19 7 . Juxtaposed against this state of agingassociated inflammation are functional impairments in innate and adaptive immune signaling, observed during vaccination of aged individuals [8][9][10][11] . Furthermore, recent human in vitro data indicates that aging results in impaired production of type I interferons in monocytes and dendritic cells following Toll-like receptor (TLR) ligation, suggesting disrupted innate immunity [12][13][14][15][16] .…”