Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort

Post vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment. At baseline, participants provided information on their demographics, recreational behaviors, and comorbid health conditions which guided our model selection process. Blood samples were collected for serum processing and spike antibody testing at each visit. Cross-sectional and longitudinal models (linear-mixed effects models) were generated to assess the relationship between selected intrinsic and extrinsic health factors on peak antibody following vaccination and to determine the influence of these predictors on antibody over time. Following cross-sectional analysis, we observed higher peak antibody titers after primary vaccination in females, those who reported recreational drug use, younger age, and prior COVID-19 history. Following booster vaccination, females and Hispanics had higher peak titers after the 3 rd and 4 th doses, respectively. Longitudinal models demonstrated that Moderna mRNA-1273 recipients, females, and those previously vaccinated had increased peak titers over time. Moreover, drug users and half-dose Moderna mRNA-1273 recipients had higher peak antibody titers over time following the first booster, while no predictive factors significantly affected post-second booster antibody responses. Overall, both intrinsic and extrinsic health factors play a significant role in shaping humoral immunogenicity after initial vaccination and the first booster. The absence of predictive factors for second booster immunogenicity suggests a more robust and consistent immune response after the second booster vaccine administration

Linear mixed-effects model for investigation of fixed effects of days since full vaccination, primary Covid-19 vaccine manufacturer, Covid-19 status, and biological sex.

Moderna mRNA-1273 recipients exhibited higher peak titers as well as more durable antibody responses when compared to Pfizer BNT162b2, as did study participants who were previously COVID-19 positive prior to vaccine recipient. Male participants, on average, demonstrated lower Ab responses when compared to female participants.</p

Post-primary vaccination mean Log₂ Ab across COVID vaccine groups.

There was no significant difference (T = 1.26, p = 0.211) between mean log2 Ab between participants who received Moderna mRNA-1273 (13.50 ± 1.71) or Pfizer BNT162b2 vaccines (13.14 ± 1.64) for their primary vaccination after 2 weeks of vaccination onset.</p

Other measured extrinsic and intrinsic health factors among the first booster vaccination sub-cohort.

Other measured extrinsic and intrinsic health factors among the first booster vaccination sub-cohort.</p

Linear mixed effects model (LMM) evaluating the relationship between post-primary vaccination antibody titers and time, COVID-19 vaccine manufacturer, prior COVID-19 infection status, and biological sex.

Linear mixed effects model (LMM) evaluating the relationship between post-primary vaccination antibody titers and time, COVID-19 vaccine manufacturer, prior COVID-19 infection status, and biological sex.</p

Post-primary vaccination mean Log₂ Ab across biological sex groups.

The mean log2 Ab in male participants (12.87 ± 12.87) was statistically lower (T = 2.47, p = 0.015) than that of female (13.56 ± 1.46) participants after primary vaccination.</p

Mean Log₂ Ab titers in primary vaccination sub-cohort with varying extrinsic and intrinsic health factors.

Mean Log2 Ab titers in primary vaccination sub-cohort with varying extrinsic and intrinsic health factors.</p

Post-primary vaccination means Log₂ Ab across age groups.

The mean log2 Ab of low age participants (13.57 ± 1.41; Tukey = A) was statistically different than elderly participants (12.61 ± 1.78; Tukey = B), but not middle-aged participants (13.36 ± 1.75; Tukey = A, B) after primary vaccination (F = 3.73; p = 0.026).</p

Mean log₂ Ab titers in first booster vaccination sub-cohort with varying extrinsic and intrinsic health factors.

Mean log2 Ab titers in first booster vaccination sub-cohort with varying extrinsic and intrinsic health factors.</p

Observed extrinsic and intrinsic health factors selected as covariates.

Observed extrinsic and intrinsic health factors selected as covariates.</p