Table_1_Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV.docx

IntroductionVaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals.
MethodsA total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis.
ResultsAt 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron.
DiscussionThis study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges.
Clinical trial registrationhttps://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.

引言：接种严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2, SARS-CoV-2）疫苗是保护个体免受新型冠状病毒肺炎（coronavirus disease 2019, COVID-19）重症侵袭的有效手段。然而，不同个体的疫苗接种免疫应答差异显著。本研究针对不同第二、三针接种间隔的人类免疫缺陷病毒感染者（people living with HIV, PLWH），动态评估其接种第三剂灭活COVID-19疫苗后的中和抗体（neutralizing antibody, NAb）应答情况。
方法：本研究共招募171名受试者：63名PLWH纳入队列1（第二剂与第三剂接种间隔为3个月），95名PLWH纳入队列2（第二剂与第三剂接种间隔为5个月），另纳入13名健康对照（healthy controls, HCs）。通过Cox回归分析，明确疫苗接种后血清转换失败的相关危险因素。
结果：第三剂接种6个月后，队列2的PLWH中和抗体几何平均浓度（geometric mean concentration, GMC）更高（64.59 vs 21.99，P < 0.0001），血清转换率也更优（68.42% vs 19.05%，P < 0.0001）。相较于野生型毒株，两个队列受试者对SARS-CoV-2德尔塔变异株（Delta variant）的中和活性均较弱，其几何平均滴度（geometric mean titer, GMT）分别为3.38和3.63（P < 0.01），而针对野生型毒株的GMT分别为13.68和14.83。所有受试者（包括健康对照与PLWH）均未产生针对奥密克戎BA.5.2（Omicron BA.5.2）的中和抗体应答。风险模型分析显示，中和抗体血清转换失败的独立危险因素为接种间隔（风险比，hazard ratio, HR=0.316，P < 0.001）与淋巴细胞计数（HR=0.409，P < 0.001）。此外，接种疫苗后发生中和抗体血清转换的PLWH，在感染奥密克戎后出现初始COVID-19症状更少。
讨论：本研究证实，当PLWH的第二、三针接种间隔更长时，第三剂灭活COVID-19疫苗可诱导更优的中和抗体应答。由于接种后发生血清转换可减轻奥密克戎感染后的症状负担，在未来奥密克戎疫情暴发期间，或许需要针对存在中和抗体血清转换失败风险因素的PLWH采取额外保护措施。
临床试验注册：本研究已在临床试验平台完成注册，注册链接为https://beta.clinicaltrials.gov/study/NCT05075070，注册号为NCT05075070。