Safety and Immunogenicity of a First-in-Human Mosquito Saliva Peptide Vaccine

NCT03055000 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 17005917-I-0059
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Mosquitos carry diseases that cause major health problems and death worldwide. The AGS-v vaccine targets proteins in mosquito saliva. This may help prevent many mosquito-borne diseases. It might also reduce the lifespan of the mosquito that bites the vaccinated person. Objective: To see if the AGS-v vaccine is safe in humans and how it affects the immune system. Eligibility: Healthy adults ages 18-50 Design: Participants will be screened another study. Participants will be randomly assigned to get either the vaccine with a booster vaccine, the vaccine without the booster, or a placebo. These are given through a needle in the upper arm. Participants will have visits that include medical history, physical exam, and blood and urine tests: Baseline: They will get the vaccine and be monitored for 2 hours. Follow-up visits 1 and 2 weeks after baseline. Visit 3 weeks after baseline: They will get the booster and be monitored for 2 hours. Follow-up visits 1 and 2 weeks after booster visit. Visit 3-5 weeks after booster visit: This includes mosquito feeding. Mosquitos grown in the lab will be allowed to bite the arm. Blood will be drawn 4 times in the 3 hours after the feeding. Phone follow-up a few days after the mosquito feeding. After the feeding visit, 5 follow-up visits about every 2 months Participants will keep a symptom diary for 7 days after each vaccine. They will record their temperature. They will measure any redness around the injection site. They will document and if possible photograph any mosquito bites they get.

Conditions

Mosquito-Borne Disease

Keywords

Mosquito-Borne Diseases; Universal Mosquito Vaccine; Mosquito Transmission; Vector Borne Viruses; Vaccine

Outcome Measures

Primary Outcomes (12)

• AEs Grade 3 or Higher

  Grade 3 or higher adverse events identified within 1 year after 2 vaccinations 21 days apart.

  1 year after vaccination (study duration)

• GM-CSF Cytokine Level as Measured by Luminex

  Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response

  21 days after last vaccination

• IL-10 Cytokine Level as Measured by Luminex

  Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response

  21 days after last vaccination

• IL-1B Cytokine Level as Measured by Luminex

  Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response

  21 days after last vaccination

• IL-2 Cytokine Level as Measured by Luminex

  Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response

  21 days after last vaccination

• IL-4 Cytokine Level as Measured by Luminex

  Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response

  21 days after last vaccination

• IL-5 Cytokine Level as Measured by Luminex

  Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response

  21 days after last vaccination

• Interferon-gamma Cytokine Level as Measured by Luminex

  Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response

  21 days after last vaccination

• Number of Subjects With 1 or More Aes

  Percent of people with an AE

  1 year after vaccination (study duration)

• Number of Subjects With 1 or More Grade 3 or Higher AE

  Percent of people with a Grade 3 or higher AE

  1 year after vaccination (study duration)

• TNF-a Cytokine Level as Measured by Luminex

  Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response

  21 days after last vaccination

• Total AGS-v Specific Immunoglobulin

  Total AGS-v specific immunoglobulin measured in serum 14 days after the first and/or second vaccination.

  21 days after last vaccination

Secondary Outcomes (14)

• GM-CSF Cytokine Level as Measured by Luminex

  60 days after Day 42 Mosquito Feeding

• IL-10 Cytokine Level as Measured by Luminex

  60 days after Day 42 Mosquito Feeding

• IL-1B Cytokine Level as Measured by Luminex

  60 days after Day 42 Mosquito Feeding

• IL-2 Cytokine Level as Measured by Luminex

  60 days after Day 42 Mosquito Feeding

• IL-4 Cytokine Level as Measured by Luminex

  60 days after Day 42 Mosquito Feeding

Study Arms (3)

AGS-v

EXPERIMENTAL

AGS-v (unadjuvanted) as a suspension in WFI (0.5mL) on Day 0 and on Day 21

Biological: AGS-v

AGS-v with adjuvant

EXPERIMENTAL

ISA-51-adjuvanted AGS-v emulsified in WFI (0.5mL)on Day 0 and on Day 21

Biological: AGS-v + adjuvant

Placebo

PLACEBO COMPARATOR

WFI (0.5mL) on Day 0 and Day 21

Other: Placebo

Interventions

AGS-v BIOLOGICAL

AGS-v (unadjuvanted) as a suspension in WFI (0.5mL) on Day 0 and on Day 21

AGS-v

AGS-v + adjuvant BIOLOGICAL

ISA-51-adjuvanted AGS-v emulsified in WFI (0.5mL) on Day 0 and on Day 21

AGS-v with adjuvant

Placebo OTHER

WFI (0.5mL) on Day 0 and Day 21

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy women and men who are greater than or equal to 18 and less than or equal to 50 years of age.
• Willingness to complete all study visits and comply with all study requirements.
• A female participant is eligible for this study if she is not pregnant or breast feeding and 1 of the following:
• Of non-child bearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year).
• Of childbearing potential but agrees to practice effective contraception or abstinence for 4 weeks prior to study initiation through 12 weeks after the second vaccine administration. Acceptable methods of contraception include a male partner who is sterile and is the sole sexual partner of the female participant or a male partner who uses a condom with spermicide plus 1 or more of the following: 1) implants of levonorgestrel; 2) injectable progestogen; 3) an intrauterine device with a documented failure rate of \<1%; 4) oral contraceptives; and 5) double barrier method including diaphragm.
• Willing to have samples stored for future research (including genetic research).
• Agrees to abstain from alcohol intake for 24 hours prior to each study visit.
• Agrees to not donate blood or blood products throughout the study.

You may not qualify if:

• Participant has any underlying or current medical condition, which, in the opinion of the Investigator, would interfere with the participation in the study.
• Individual with body mass index (BMI) less than or equal to 18 and greater than or equal to 40.
• Participants who have a clinically significant (as determined by the PI) baseline Grade 1 or greater toxicity, or any Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity table.
• Receipt of blood or blood products (including immunoglobulins) within 3 months prior to enrollment.
• Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is greater) prior to enrollment.
• Receipt of any unlicensed vaccine within 6 months prior to enrollment.
• Self-reported or known history of alcoholism or drug abuse within 6 months prior to enrollment, or positive urine/serum test for drugs of abuse at screening
• Self-reported or known history of psychiatric or psychological issues that require treatment and are deemed by the PI to be a contraindication to protocol participation.
• History of a previous severe allergic reaction with generalized urticaria, angioedema, anaphylaxis or anaphylactoid reaction.
• Any condition or event that, in the judgment of the PI, is a contraindication to protocol participation or impairs the volunteer's ability to give informed consent.
• Has a known allergy to any of the components of the vaccine.
• Has a history of severe immunization reaction.
• Has a severe allergic reaction to mosquito bites

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Peng Z, Yang M, Simons FE. Immunologic mechanisms in mosquito allergy: correlation of skin reactions with specific IgE and IgG antibodies and lymphocyte proliferation response to mosquito antigens. Ann Allergy Asthma Immunol. 1996 Sep;77(3):238-44. doi: 10.1016/S1081-1206(10)63262-0.

  PMID: 8814051 BACKGROUND

• Sidjanski S, Vanderberg JP. Delayed migration of Plasmodium sporozoites from the mosquito bite site to the blood. Am J Trop Med Hyg. 1997 Oct;57(4):426-9. doi: 10.4269/ajtmh.1997.57.426.

  PMID: 9347958 BACKGROUND

• Ribeiro JM. Role of saliva in blood-feeding by arthropods. Annu Rev Entomol. 1987;32:463-78. doi: 10.1146/annurev.en.32.010187.002335. No abstract available.

  PMID: 2880553 BACKGROUND

• Manning JE, Oliveira F, Coutinho-Abreu IV, Herbert S, Meneses C, Kamhawi S, Baus HA, Han A, Czajkowski L, Rosas LA, Cervantes-Medina A, Athota R, Reed S, Mateja A, Hunsberger S, James E, Pleguezuelos O, Stoloff G, Valenzuela JG, Memoli MJ. Safety and immunogenicity of a mosquito saliva peptide-based vaccine: a randomised, placebo-controlled, double-blind, phase 1 trial. Lancet. 2020 Jun 27;395(10242):1998-2007. doi: 10.1016/S0140-6736(20)31048-5. Epub 2020 Jun 11.

  PMID: 32534628 DERIVED

MeSH Terms

Conditions

Mosquito-Borne Diseases

Interventions

Adjuvants, Pharmaceutic

Condition Hierarchy (Ancestors)

Vector Borne Diseases; Infections

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Results Point of Contact

• Title: Memoli, Matthew
• Organization: National Institute of Allergy and Infectious Diseases

mm982v@nih.gov

+1 301 443 5971

Study Officials

• Matthew J Memoli, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2017
• First Posted: February 16, 2017
• Study Start: February 15, 2017
• Primary Completion: December 28, 2018
• Study Completion: December 28, 2018
• Last Updated: August 11, 2020
• Results First Posted: August 3, 2020

Record last verified: 2018-12

Locations

US (1)