Adjusted booster schedules disperse age-dependent differences in antibody titers benefitting risk populations

Müller, Lisa; Andrée, Marcel; Moskorz, Wiebke; Drexler, Ingo; Hauka, Sandra; Ptok, Johannes; Walotka, Lara; Grothmann, Ramona; Hillebrandt, Jonas; Ritchie, Anastasia; Peter, Laura; Walker, Andreas; Timm, Jörg; Adams, Ortwin; Schaal, Heiner

doi:10.1101/2022.08.08.22278545

Cited by 3 publications

(3 citation statements)

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“…Another study also reported consistently lower antibody titer level post-vaccination for PLWH at multiple time points; however, the median age of PLWH in the study was 54 years compared to 30 years in the comparators (24). Their results could have been affected by age imbalance between the groups since evidence suggests older individuals have lower quantitative anti-spike IgG after vaccination (25).…”

Section: Discussionmentioning

confidence: 74%

No difference in anti-spike antibody and surrogate viral neutralization following SARS-CoV-2 booster vaccination in persons with HIV compared to controls (CO-HIV Study)

et al. 2023

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BackgroundUnderstanding the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination will enable accurate counseling and inform evolving vaccination strategies. Little is known about antibody response following booster vaccination in people living with HIV (PLWH).MethodsWe enrolled SARS-CoV-2 vaccinated PLWH and controls without HIV in similar proportions based on age and comorbidities. Participants completed surveys on prior SARS-CoV-2 infection, vaccination, and comorbidities, and provided self-collected dried blood spots (DBS). Quantitative anti-spike IgG and surrogate viral neutralization assays targeted wild-type (WT), Delta, and Omicron variants. We also measured quantitative anti-nucleocapsid IgG. The analysis population had received full SARS-CoV-2 vaccination plus one booster dose. Bivariate analyses for continuous outcomes utilized Wilcoxon tests and multivariate analysis used linear models.ResultsThe analysis population comprised 140 PLWH and 75 controls with median age 58 and 55 years, males 95% and 43%, and DBS collection on 112 and 109 days after the last booster dose, respectively. Median CD4 count among PLWH was 760 cells/mm3 and 91% had an undetectable HIV-1 viral load. Considering WT, Delta, and Omicron variants, there was no significant difference in mean quantitative anti-spike IgG between PLWH (3.3, 2.9, 1.8) and controls (3.3, 2.9, 1.8), respectively (p-values=0. 771, 0.920, 0.708). Surrogate viral neutralization responses were similar in PLWH (1.0, 0.9, and 0.4) and controls (1.0, 0.9, 0.5), respectively (p-values=0.594, 0.436, 0.706).ConclusionsPLWH whose CD4 counts are well preserved and persons without HIV have similar anti-spike IgG antibody levels and viral neutralization responses after a single SARS-CoV-2 booster vaccination.

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Section: Discussionmentioning

confidence: 74%

No difference in anti-spike antibody and surrogate viral neutralization following SARS-CoV-2 booster vaccination in persons with HIV compared to controls (CO-HIV Study)

et al. 2023

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“…Five (50,53,57,59, 70) of the nine trials included for the efficacy analysis suggested lower efficacy in older adults than in younger adults, reflecting that of Cheng et al (38) This discrepancy could be attributed to comorbidities and immunosenescence (typically defined as age-related structural and functional changes in the body's innate and adaptive immune system) (78, 81). Older adults thus have poorer immune responses to COVID-19 vaccines than younger ones (32,82). It likewise explains that serum neutralizing and binding antibodies decreased with age in the elderly cohort and were significantly lower in those ≥ 80 years old (83).…”

Section: Discussionmentioning

confidence: 96%

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

Liu

et al. 2022

Front. Immunol.

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BackgroundOlder adults are more susceptible to severe health outcomes for coronavirus disease 2019 (COVID-19). Universal vaccination has become a trend, but there are still doubts and research gaps regarding the COVID-19 vaccination in the elderly. This study aimed to investigate the efficacy, immunogenicity, and safety of COVID-19 vaccines in older people aged ≥ 55 years and their influencing factors.MethodsRandomized controlled trials from inception to April 9, 2022, were systematically searched in PubMed, EMBASE, the Cochrane Library, and Web of Science. We estimated summary relative risk (RR), rates, or standardized mean difference (SMD) with 95% confidence interval (CI) using random-effects meta-analysis. This study was registered with PROSPERO (CRD42022314456).ResultsOf the 32 eligible studies, 9, 21, and 25 were analyzed for efficacy, immunogenicity, and safety, respectively. In older adults, vaccination was efficacious against COVID-19 (79.49%, 95% CI: 60.55−89.34), with excellent seroconversion rate (92.64%, 95% CI: 86.77−96.91) and geometric mean titer (GMT) (SMD 3.56, 95% CI: 2.80−4.31) of neutralizing antibodies, and provided a significant protection rate against severe disease (87.01%, 50.80−96.57). Subgroup and meta-regression analyses consistently found vaccine types and the number of doses to be primary influencing factors for efficacy and immunogenicity. Specifically, mRNA vaccines showed the best efficacy (90.72%, 95% CI: 86.82−93.46), consistent with its highest seroconversion rate (98.52%, 95% CI: 93.45−99.98) and GMT (SMD 6.20, 95% CI: 2.02−10.39). Compared to the control groups, vaccination significantly increased the incidence of total adverse events (AEs) (RR 1.59, 95% CI: 1.38−1.83), including most local and systemic AEs, such as pain, fever, chill, etc. For inactivated and DNA vaccines, the incidence of any AEs was similar between vaccination and control groups (p > 0.1), while mRNA vaccines had the highest risk of most AEs (RR range from 1.74 to 7.22).ConclusionCOVID-19 vaccines showed acceptable efficacy, immunogenicity and safety in older people, especially providing a high protection rate against severe disease. The mRNA vaccine was the most efficacious, but it is worth surveillance for some AEs it caused. Increased booster coverage in older adults is warranted, and additional studies are urgently required for longer follow-up periods and variant strains.

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“…Faster production of both total and RBD-specific IgG has been observed in female patients (28, 29), and early upregulation of specific IgM responses (24,30) and neutralising RBD specific responses (31) have been associated with improved disease outcome. In response to vaccination, elderly patients generate weaker humoral responses, characterised by slower induction of antibody production, lower magnitude Ab titres at peak and quicker Ab decline, when compared to younger adults (32)(33)(34)(35). Whilst several reports have shown that elderly patients are able to generate robust and neutralising antibody responses during acute infection (7,36,37), there is less evidence of early antibody kinetics impacting on disease outcome in elderly patients.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study

Parker

Thomas²,

Roper³

et al. 2023

Front. Immunol.

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The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.

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Adjusted booster schedules disperse age-dependent differences in antibody titers benefitting risk populations

Cited by 3 publications

References 21 publications

No difference in anti-spike antibody and surrogate viral neutralization following SARS-CoV-2 booster vaccination in persons with HIV compared to controls (CO-HIV Study)

No difference in anti-spike antibody and surrogate viral neutralization following SARS-CoV-2 booster vaccination in persons with HIV compared to controls (CO-HIV Study)

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

SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study

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