Cohort intrinsic health factor summary table.

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 3rd and 4th 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.

新冠mRNA疫苗接种诱导的疫苗免疫应答，可能受外在（可控）或内在（固有）健康因素驱动。因此，本研究探讨了外在与内在健康因素对新冠疫苗基础免疫后抗体峰值应答的影响，以及抗体峰值水平与持久性随时间变化的轨迹。本纵向队列的参与者在入组后每3个月接受一次随访，随访周期最长达2年。基线阶段，参与者提供了人口统计学特征、娱乐行为与合并健康状况等信息，为本次研究的模型筛选流程提供了依据。每次随访均采集血液样本，用于血清制备与刺突蛋白抗体检测。本研究构建了横断面模型与纵向模型（线性混合效应模型，linear-mixed effects models），以评估筛选出的外在与内在健康因素与疫苗接种后抗体峰值应答之间的关联，并明确上述预测因素随时间对抗体水平的影响。横断面分析结果显示，女性、有娱乐性药物使用史、年龄较小以及既往新冠病毒感染史的参与者，在基础免疫后抗体峰值滴度更高。加强针接种后，女性在第3剂加强针接种后、西班牙裔参与者在第4剂加强针接种后分别呈现更高的抗体峰值滴度。纵向模型分析结果显示，接种莫德纳mRNA-1273疫苗的参与者、女性以及既往接种过疫苗的参与者，其抗体峰值滴度随时间呈上升趋势。此外，在首次加强针接种后，药物使用者与接种半剂量莫德纳mRNA-1273疫苗的参与者，其抗体峰值滴度随时间持续处于较高水平；而第二次加强针接种后的抗体应答未受任何预测因素的显著影响。总体而言，外在与内在健康因素均对基础免疫及首次加强针接种后的体液免疫原性具有显著调控作用。第二次加强针的免疫原性未发现显著预测因素，这提示第二次加强针接种后机体可产生更强且更稳定的免疫应答。