Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial

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-naive 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 x 20 mu g; standard); all other groups received adjuvanted PXVX0317: groups 2-4 received two doses 28 days apart (2 x 6 mu g [group 2], 2 x 10 mu g [group 3], or 2 x 20 mu g [group 4]; standard); group 4 also received a booster dose 18 months after the first active injection (40 mu g; standard plus booster); groups 5-7 received two doses 14 days apart (2 x 6 mu g [group 5], 2 x 10 mu g [group 6], or 2 x 20 mu g [group 7]; accelerated); and group 8 received one dose (1 x 40 mu g; 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 mu g injection of adjuvanted PXVX0317 is being further investigated in phase 3 clinical trials (NCT05072080 and NCT05349617). Copyright (c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

The study evaluated the safety and immunogenicity of the aluminum hydroxide-adjuvanted PXVX0317 vaccine. The results showed that PXVX0317 vaccine was well tolerated and induced a robust and durable immune response against CHIKV.