Bennett Chijioke, Hoosain Zaheer, Koen Anthonet, Lalloo Umesh, Louw Cheryl, Maluleke Vongane, Patel Faeezah, Benade Gabriella, Venter Esme Louise, Galbiati Shirley, Shinde Vivek, Madhi Shabir A
Novavax, Inc., 700 Quince Orchard Road, Gaithersburg, MD 20878, USA.
Josha Research, 28 East Burger Street, Bloemfontein 9301, South Africa.
J Infect. 2024 Dec;89(6):106285. doi: 10.1016/j.jinf.2024.106285. Epub 2024 Sep 27.
Response data for COVID-19 vaccines in immunosuppressed individuals are typically limited to standard dosing in small populations. Adjusting number or interval of doses may impact immune responses based on HIV status.
This phase 2 randomised, observer-blinded, placebo-controlled South African study (2019nCoV-505/NCT05112848) enrolled medically stable people living with HIV (PLWH) and HIV-uninfected participants aged 18-65 years. PLWH were randomised 1:1:1 to receive NVX-CoV2373 on day 0 (D0) and either D21 (2-Dose) or D70 (2-Dose), or on D0, D21, and D70 (3-Dose). HIV-uninfected participants were randomised 1:1 to each 2-Dose regimen. PLWH were stratified into well-controlled and less-well-controlled subgroups. The primary immunologic endpoint included serum IgG and neutralising antibody responses (per geometric mean fold rise [GMFR] in titre and seroconversion rate) to ancestral SARS-CoV-2 at D35 (2-Dose) and D84 (2-Dose and 3-Dose). The primary safety endpoints were participants with an unsolicited adverse event through D84, at D120, and at D180, or reactogenicity ≤7 days post-vaccination.
Of 288 PLWH, 98, 96, and 94 were randomised into the 2-Dose, 2-Dose, and 3-Dose groups, respectively; 96 HIV-uninfected participants were randomised to the 2-Dose (n = 47) or 2-Dose (n = 49) regimens. Most (>85%) of the population were SARS-CoV-2 positive at baseline. Ancestral anti-spike IgG GMFRs in PLWH and HIV-uninfected participants, respectively, were 12·4 and 12·9 (D35) and 12·2 and 13·6 (D84). Comparable outcomes occurred across dosing regimens and in well-controlled and less-well-controlled PLWH. Microneutralization GMFRs at D84 in PLWH and HIV-uninfected participants, respectively, were: 6·9 and 10·1 (2-Dose), 11·0 and 11·3 (2-Dose), and 17·2 (PLWH 3-Dose). Antibody responses against BA.1 trended similar to those against the ancestral virus. Safety outcomes were comparable among PLWH and HIV-uninfected participants.
This study demonstrated that NVX-CoV2373 produced consistent immunogenicity responses to SARS-CoV-2 among PLWH and HIV-uninfected participants, with no new safety signals.
免疫功能低下个体中新冠疫苗的反应数据通常限于小群体中的标准剂量。根据艾滋病毒感染状况调整剂量数量或间隔可能会影响免疫反应。
这项2期随机、观察者盲法、安慰剂对照的南非研究（2019nCoV-505/NCT05112848）纳入了年龄在18至65岁之间、病情医学稳定的艾滋病毒感染者（PLWH）和未感染艾滋病毒的参与者。PLWH按1:1:1随机分组，在第0天（D0）接受NVX-CoV2373，并在第21天（2剂方案）或第70天（2剂方案）接种，或在D0、D21和D70接种（3剂方案）。未感染艾滋病毒的参与者按1:1随机分配到每种2剂方案。PLWH被分层为控制良好和控制欠佳的亚组。主要免疫终点包括在第35天（2剂方案）和第84天（2剂和3剂方案）时针对原始SARS-CoV-2的血清IgG和中和抗体反应（根据滴度的几何平均倍数升高[GMFR]和血清转化率）。主要安全终点是在第84天、第120天和第180天出现非预期不良事件的参与者，或接种疫苗后≤7天的反应原性。
在288名PLWH中，分别有98、96和94人被随机分配到2剂方案组、2剂方案组和3剂方案组；96名未感染艾滋病毒的参与者被随机分配到2剂方案组（n = 47）或2剂方案组（n = 49）。大多数（>85%）研究对象在基线时SARS-CoV-2呈阳性。PLWH和未感染艾滋病毒参与者中，原始抗刺突IgG的GMFR分别为12.4和12.9（第35天）以及12.2和13.6（第84天）。不同给药方案以及控制良好和控制欠佳的PLWH中均出现了类似的结果。PLWH和未感染艾滋病毒参与者在第84天的微量中和GMFR分别为：（2剂方案）6.9和10.1、（2剂方案）11.0和11.3，以及（PLWH 3剂方案）17.2。针对BA.1的抗体反应趋势与针对原始病毒的反应相似。PLWH和未感染艾滋病毒参与者的安全结果相当。
本研究表明，NVX-CoV2373在PLWH和未感染艾滋病毒的参与者中对SARS-CoV-2产生了一致的免疫原性反应，且无新的安全信号。
