Immunogenicity and safety following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-MTM adjuvant (NVX-CoV2373) versus a primary series in people living with and without HIV-1 infection in South Africa: A randomized crossover phase 2a/2b trial

Abstract

COVID-19 remains a global public health issue and an improved understanding of vaccine performance in immunocompromised individuals, including people living with HIV (PLWH), is needed. Initial data from the present study's pre-crossover/booster phase were previously reported. This phase 2a/b clinical trial in South Africa (2019nCoV-501/NCT04533399) revisits 1:1 randomly assigned HIV-negative adults (18-84 years) and medically stable PLWH (18-64 years) who previously received two NVX-CoV2373 doses (5 μg recombinant Spike protein with 50 μg Matrix-M™ adjuvant) or placebo. During the 6-month blinded crossover/booster phase, NVX-CoV2373 recipients could receive a single NVX-CoV2373 booster dose and placebo recipients a 2-dose NVX-CoV2373 primary series. NVX-CoV2373 safety and immunogenicity were assessed according to prior SARS-CoV-2 infection and HIV status. Post-crossover, 1900/3793 NVX-CoV2373 recipients were assigned another dose, and 1893/3793 placebo recipients were assigned NVX-CoV2373 primary series. Approximately 56% of the participants were SARS-CoV-2-seropositive ("seropositive") at crossover (6% PLWH). In seropositive participants (HIV-negative and PLWH), booster-dose anti-spike IgG, MN₅₀ and hACE2 inhibition responses increased to similar levels, exceeding those in seronegative participants. In primary-series and booster cohorts, seronegative PLWH showed higher neutralizing responses (4.9- to 5.5-fold, respectively) versus peak pre-crossover primary-series responses. The safety profile was similar among the pre-crossover/booster phase groups; solicited and unsolicited adverse events were infrequent in all groups. A single NVX-CoV2373 booster dose substantially increased antibodies. All baseline seropositive participants showed higher immune responses than seronegative participants. These findings support use of NVX-CoV2373, including in immunocompromised individuals.

Keywords: Novavax, Inc.; and the Coalition for Epidemic Preparedness Innovations; the Bill & Melinda Gates Foundation.

Figure 1.

CONSORT diagram. Abbreviations: PLWH, people living with HIV.

Figure 2.

Neutralizing antibody activity to wild-type SARS-CoV-2 by study day (log scale). Levels of NAbs to wild-type SARS-CoV-2 (measured by the microneutralisation assay) were assessed for all participants, hiv-negative participants only, and PLWH only, stratified by SARS-CoV-2 serostatus. GMTs with 95% CI are shown; error bars smaller than the size of the graphed symbol are not visible. Serostatus was assessed at baseline, and points from Day 0 to the first measurement of Day 201 on each graph are based on baseline serostatus. On Day 201, serostatus was reassessed because some participants became seropositive during the pre-crossover phase. Points on each graph from the second instance of Day 201 to Day 236 are based on this reassessed serostatus. The number of participants in each group is shown for each time point below the graphs. Abbreviations: CI, confidence interval; GMT, geometric mean titer; NAbs, neutralizing antibodies; PLWH, people living with HIV.