Safety and immunogenicity of AGS-v PLUS, a mosquito saliva peptide vaccine against arboviral diseases: A randomized, double-blind, placebo-controlled Phase 1 trialResearch in context
DeAnna J. Friedman-Klabanoff,
Megan Birkhold,
Mara T. Short,
Timothy R. Wilson,
Claudio R. Meneses,
Joshua R. Lacsina,
Fabiano Oliveira,
Shaden Kamhawi,
Jesus G. Valenzuela,
Sally Hunsberger,
Allyson Mateja,
Gregory Stoloff,
Olga Pleguezuelos,
Matthew J. Memoli,
Matthew B. Laurens
Affiliations
DeAnna J. Friedman-Klabanoff
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA
Megan Birkhold
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA
Mara T. Short
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
Timothy R. Wilson
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
Claudio R. Meneses
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
Joshua R. Lacsina
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
Fabiano Oliveira
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
Shaden Kamhawi
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
Jesus G. Valenzuela
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
Sally Hunsberger
Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
Allyson Mateja
Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA
Gregory Stoloff
PepTcell (t/a SEEK), London, United Kingdom
Olga Pleguezuelos
ConserV Bioscience, Oxfordshire, United Kingdom
Matthew J. Memoli
Clinical Studies Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Matthew B. Laurens
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA; Corresponding author. Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St, Rm 480, Baltimore, MD, 21201, USA.
Summary: 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.
