Safety and immunogenicity of AGS-v PLUS, a mosquito saliva peptide vaccine against arboviral diseases: A randomized, double-blind, placebo-controlled Phase 1 trial.

Background: Immunity to mosquito salivary proteins could provide protection against multiple mosquito-borne diseases and significantly impact public health. We evaluated the safety and immunogenicity of AGS-v PLUS, a mosquito salivary peptide vaccine, in healthy adults 18-50 years old.
Methods: We conducted a randomized, double-blind, placebo-controlled Phase 1 study of AGS-v PLUS administered subcutaneously on Days 1 and 22 at the Center for Vaccine Development and Global Health, Baltimore, MD, USA. Participants were block randomized 1:1:1:1:1 to two doses saline placebo, two doses AGS-v PLUS, AGS-v PLUS/ISA-51 and saline placebo, two doses AGS-v PLUS/ISA-51, or two doses AGS-v PLUS/Alhydrogel. Primary endpoints were safety (all participants receiving ≥1 injection) and antibody and cytokine responses (all participants with day 43 samples), analysed by intention to treat.
Findings: Between 26 August 2019 and 25 February 2020, 51 participants were enrolled and randomized, 11 into the single dose AGS-v PLUS/ISA-51 group and ten in other groups. Due to COVID-19, 15 participants did not return for day 43 samplings. Participants experienced no treatment-emergent or serious adverse events. All solicited symptoms in 2/10 placebo recipients and 22/41 AGS-v PLUS recipients after dose one and 1/10 placebo recipients and 22/41 AGS-v PLUS recipients after dose two were mild/moderate except for one severe fever the day after vaccination (placebo group). Only injection site pain was more common in vaccine groups (15/51 after dose 1 and 11/51 after dose 2) versus placebo. Compared to placebo, all vaccine groups had significantly greater fold change in anti-AGS-v PLUS IgG and IFN-ɣ from baseline.
Interpretation: AGS-v PLUS had favourable safety profile and induced robust immune responses. Next steps will determine if findings translate into clinical efficacy against mosquito-borne diseases.
Funding: UK Department of Health and Social Care.
Competing Interests: Declaration of interests The views expressed in this publication are those of the author(s) and not necessarily those of Innovate UK or the UK's Department of Health and Social Care. Imutex Limited is a joint venture with PepTcell Limited (trading as SEEK) in which Open Orphan has a 49% shareholding, and PepTcell has 51%. Dr. Olga Pleguezuelos is an employee of ConserV Bioscience, a subsidiary of PepTcell Limited (trading as SEEK) and a shareholder in PepTcell Limited (trading as SEEK). Gregory Stoloff is an employee and shareholder in PepTcell. Imutex Ltd owns the intellectual property rights around AGS-v and AGS-v PLUS. All remaining authors declare no conflicts of interest. OP and GS are also named inventors in the following issued patents: AU 2008297213, AU 2013200258, BE 2783694, CH 2783694, CN 20101815526, DE 602008054283.1, DK 2783694, EP 2783694, ES 2783694, FI 2783694, FR 2783694, GB 2783694, IE 2783694, IN 296636, IT 2783694, JP 5981883, JP 6227018, MC 2783694, MT 2783694, MX 310667, NO 2783694, NZ 602090, OA 14958, PL 2783694, PT 2783694, RU 2466737, SE 2783694, SG 187401, TR 2783694, TW 548646, US 8,986,703, ZA 2010/00914.
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