Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial. Issue 9 (September 2022)

• Record Type: Journal Article
• Authors: Bennett, Sean R; McCarty, James M; Ramanathan, Roshan; Mendy, Jason; Richardson, Jason S; Smith, Jonathan; Alexander, Jeff; Ledgerwood, Julie E; de Lame, Paul-André; Royalty Tredo, Sarah; Warfield, Kelly L; Bedell, Lisa
• Is Part Of: Lancet infectious diseases. Volume 22:Issue 9(2022)
• Page Start: 1343
• Page End: 1355
• Publication Date: 2022-09
• Subjects: Communicable diseases -- Periodicals; Infection -- Periodicals; Communicable Diseases -- Periodicals; Infection -- Periodicals; Maladies infectieuses -- Périodiques; Infection -- Périodiques; Communicable diseases; Infection; Periodicals; 616.905
• DOI: 10.1016/S1473-3099(22)00226-2
• Languages: English
• ISSNs: 1473-3099

Abstract

Summary: Background: Chikungunya virus (CHIKV) disease is an ongoing public health threat. We aimed to evaluate the safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted formulation of a CHIKV virus-like particle (VLP) vaccine. Methods: This randomised, double-blind, parallel-group, phase 2 trial was conducted at three clinical trial centres in the USA. Eligible participants were healthy CHIKV-naïve adults aged 18–45 years. Participants were stratified by site and randomly assigned (1:1:1:1:1:1:1:1) to one of the eight vaccination groups using a block size of 16. Group 1 received two doses of unadjuvanted PXVX0317 28 days apart (2 × 20 μg; standard); all other groups received adjuvanted PXVX0317: groups 2–4 received two doses 28 days apart (2 × 6 μg [group 2], 2 × 10 μg [group 3], or 2 × 20 μg [group 4]; standard); group 4 also received a booster dose 18 months after the first active injection (40 μg; standard plus booster); groups 5–7 received two doses 14 days apart (2 × 6 μg [group 5], 2 × 10 μg [group 6], or 2 × 20 μg [group 7]; accelerated); and group 8 received one dose (1 × 40 μg; single). The primary endpoint was the geometric mean titre of anti-CHIKV neutralising antibody on day 57 (28 days after the last vaccination), assessed in the immunogenicity-evaluable population. Additionally, we assessed safety. This trial is registered at ClinicalTrials.gov, NCT03483961 . Findings: This trial was conducted from April 18, 2018, to Sept 21, 2020; 468 participants were assessed for eligibility. Of these, 415 participants were randomly assigned to eight groups (n=53 in groups 1, 5, and 6; n=52 in groups 2 and 8; n=51 in groups 3 and 7; and n=50 in group 4) and 373 were evaluable for immunogenicity. On day 57, serum neutralising antibody geometric mean titres were 2057·0 (95% CI 1584·8–2670·0) in group 1, 1116·2 (852·5–1461·4; p=0·0015 vs group 1 used as a reference) in group 2, 1465·3 (1119·1–1918·4; p=0·076) in group 3, 2023·8 (1550·5–2641·7; p=0·93) in group 4, 920·1 (710·9–1190·9; p<0·0001) in group 5, 1206·9 (932·4–1562·2; p=0·0045) in group 6, 1562·8 (1204·1–2028·3; p=0·14) in group 7, and 1712·5 (1330·0–2205·0; p=0·32) in group 8. In group 4, a booster dose increased serum neutralising antibody geometric mean titres from 215·7 (95% CI 160·9–289·1) on day 547 to 10 941·1 (7378·0–16 225·1) on day 575. Durability of the immune response (evaluated in groups 1, 4, and 8) was shown up to 2 years. The most common solicited adverse event was pain at the injection site, reported in 12 (23%) of 53 participants who received the unadjuvanted vaccine (group 1) and 111 (31%) of 356 who received the adjuvanted vaccine. No vaccine-related serious adverse events were reported. Interpretation: PXVX0317 was well tolerated and induced a robust and durable serum neutralising antibody immune response against CHIKV up to 2 years. A single 40 μg injection of adjuvanted PXVX0317 is being further investigated in phase 3 clinical trials (NCT05072080 and NCT05349617 ). Funding: Emergent BioSolutions.