Immunogenicity and safety of SARS-CoV-2 recombinant spike protein vaccine in South African people living with and without HIV-1 infection: A phase 2 randomised trial

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection Pub Date : 2024-09-27 DOI:10.1016/j.jinf.2024.106285

Chijioke Bennett , Zaheer Hoosain , Anthonet Koen , Umesh Lalloo , Cheryl Louw , Vongane Maluleke , Faeezah Patel , Gabriella Benade , Esme Louise Venter , Shirley Galbiati , Vivek Shinde , Shabir A. Madhi , on behalf of the Study 2019nCoV-505 Investigators Group

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引用次数: 0

Abstract

Background

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.

Methods

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_D0/D21) or D70 (2-Dose_D0/D70), 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_D0/D21) and D84 (2-Dose_D0/D70 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.

Results

Of 288 PLWH, 98, 96, and 94 were randomised into the 2-Dose_D0/D21, 2-Dose_D0/D70, and 3-Dose groups, respectively; 96 HIV-uninfected participants were randomised to the 2-Dose_D0/D21 (n = 47) or 2-Dose_D0/D70 (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_D0/D21), 11·0 and 11·3 (2-Dose_D0/D70), 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.

Conclusion

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.

查看原文本刊更多论文

南非 HIV-1 感染者和非 HIV-1 感染者接种 SARS-CoV-2 重组尖峰蛋白疫苗的免疫原性和安全性：2 期随机试验。

背景：COVID-19疫苗在免疫抑制个体中的应答数据通常仅限于小群体中的标准剂量。根据艾滋病病毒感染状况调整剂量的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、安慰剂对照南非研究（2019nCoV-505/NCT05112848）招募了年龄在 18-65 岁、病情稳定的 HIV 感染者（PLWH）和未感染 HIV 的参与者。HIV感染者按1:1:1随机分配，在第0天（D0）和第21天（2-剂量D0/D21）或第70天（2-剂量D0/D70）接受NVX-CoV2373，或在第0天、第21天和第70天（3-剂量）接受NVX-CoV2373。未感染艾滋病毒的参与者按 1:1 随机分配到每种 2 剂量方案中。艾滋病毒感染者被分为控制良好亚组和控制较差亚组。主要免疫学终点包括在D35（2-DoseD0/D21）和D84（2-DoseD0/D70和3-Dose）对祖先SARS-CoV-2的血清IgG和中和抗体反应（滴度的几何平均倍数上升[GMFR]和血清转换率）。主要安全性终点是在D84、D120和D180期间出现主动不良事件或接种后7天内出现反应性的参与者：在288名艾滋病毒感染者中，分别有98人、96人和94人被随机分配到2剂量D0/D21组、2剂量D0/D70组和3剂量组；96名未感染艾滋病毒的参与者被随机分配到2剂量D0/D21组（47人）或2剂量D0/D70组（49人）。大多数人（>85%）在基线时为 SARS-CoV-2 阳性。PLWH 和 HIV 未感染者的祖先抗尖峰抗体 IgG GMFR 分别为 12-4 和 12-9 (D35)，以及 12-2 和 13-6 (D84)。不同给药方案、控制良好和控制较差的艾滋病毒感染者的结果具有可比性。感染艾滋病毒的 PLWH 和未感染艾滋病毒的参与者在 D84 时的微中性 GMFR 分别为 6-9 和 10-1 （2-D）：6-9和10-1（2-剂量D0/D21）、11-0和11-3（2-剂量D0/D70）以及17-2（PLWH 3-剂量）。针对 BA.1 的抗体反应与针对祖先病毒的抗体反应趋势相似。感染艾滋病毒的 PLWH 和未感染艾滋病毒的参与者的安全性结果相当：这项研究表明，NVX-CoV2373 能在 PLWH 和未感染 HIV 的参与者中产生一致的针对 SARS-CoV-2 的免疫原性反应，而且没有新的安全性信号：Novavax, Inc.

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来源期刊

Journal of Infection 医学-传染病学

CiteScore

45.90

自引率

3.20%

发文量

475

审稿时长

16 days

期刊介绍： The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection. Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.