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

Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study in Healthy Volunteers to Evaluate the Safety and Immunogenicity of AGS-v, a Universal Mosquito-Borne Disease Vaccine

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.

Study Overview

Detailed Description

Mosquito-borne diseases continue to cause significant morbidity and mortality worldwide despite on-going control efforts. In 2015, there were >200 million cases of malaria worldwide, causing nearly half a million deaths, with most of the deaths occurring among children under the age of 5 years. Mosquitos also transmit arboviruses, including dengue, yellow fever, West Nile virus, chikungunya, Rift Valley fever, Japanese encephalitis, and Zika virus. The current new outbreak of Zika virus in Central and South America, as well as the Caribbean, serves as a reminder of how quickly these viruses can spread and how difficult they can be to control.

In this protocol we plan to perform a Phase I study of a novel universal mosquito-borne disease vaccine. Through modulation of the immune system after a mosquito feeding, this vaccine targets the vector saliva and may provide prophylaxis against multiple arboviral and protozoal diseases. In addition the vaccine potentially leads to a reduced mosquito lifespan after feeding therefore also reducing transmission of these diseases.

In this protocol we hope to demonstrate the safety of this vaccine similar to SEEK s other peptide based vaccines Flu-v and HIV-v that have been found to have very good safety profiles in previous Phase I trials. We also hope to demonstrate immunomodulation after a controlled clean Aedes aegypti mosquito feeding to demonstrate proof of concept efficacy of the vaccine. With the current rise of Zika in the Americas and the threat of local mosquito transmission in the U.S. and the rest of the world, a successful universal mosquito-borne disease vaccine offers the benefit of targeting this emerging disease as well as the many established infections such as dengue and malaria that make dealing with this newly emerging epidemic a challenge.

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

-INCLUSION CRITERIA:

  1. Healthy women and men who are greater than or equal to 18 and less than or equal to 50 years of age.
  2. Willingness to complete all study visits and comply with all study requirements.
  3. A male subject is eligible for the study if he agrees to practicing abstinence or using a condom with spermicide plus an acceptable form of contraception (see inclusion criteria 4) being used by any female partner from 4 weeks before study start to 12 weeks after the second vaccine administration.
  4. 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.
  5. Willing to have samples stored for future research (including genetic research).
  6. Agrees to abstain from alcohol intake for 24 hours prior to each study visit.
  7. Agrees to not donate blood or blood products throughout the study.

EXCLUSION CRITERIA:

  1. Participant has any underlying or current medical condition, which, in the opinion of the Investigator, would interfere with the participation in the study.
  2. Individual with body mass index (BMI) less than or equal to 18 and greater than or equal to 40.
  3. 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.
  4. Receipt of blood or blood products (including immunoglobulins) within 3 months prior to enrollment.
  5. Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is greater) prior to enrollment.
  6. Receipt of any unlicensed vaccine within 6 months prior to enrollment.
  7. 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
  8. 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.
  9. History of a previous severe allergic reaction with generalized urticaria, angioedema, anaphylaxis or anaphylactoid reaction.
  10. 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.
  11. Has a known allergy to any of the components of the vaccine.
  12. Has a history of severe immunization reaction.
  13. Has a severe allergic reaction to mosquito bites

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AGS-v
AGS-v (unadjuvanted) as a suspension in WFI (0.5mL) on Day 0 and on Day 21
AGS-v (unadjuvanted) as a suspension in WFI (0.5mL) on Day 0 and on Day 21
Experimental: AGS-v with adjuvant
ISA-51-adjuvanted AGS-v emulsified in WFI (0.5mL)on Day 0 and on Day 21
ISA-51-adjuvanted AGS-v emulsified in WFI (0.5mL) on Day 0 and on Day 21
Placebo Comparator: Placebo
WFI (0.5mL) on Day 0 and Day 21
WFI (0.5mL) on Day 0 and Day 21

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AEs Grade 3 or Higher
Time Frame: 1 year after vaccination (study duration)
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
Time Frame: 21 days after last vaccination
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
Time Frame: 21 days after last vaccination
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
Time Frame: 21 days after last vaccination
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
Time Frame: 21 days after last vaccination
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
Time Frame: 21 days after last vaccination
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
Time Frame: 21 days after last vaccination
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
Time Frame: 21 days after last vaccination
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
Time Frame: 1 year after vaccination (study duration)
Percent of people with an AE
1 year after vaccination (study duration)
Number of Subjects With 1 or More Grade 3 or Higher AE
Time Frame: 1 year after vaccination (study duration)
Percent of people with a Grade 3 or higher AE
1 year after vaccination (study duration)
TNF-a Cytokine Level as Measured by Luminex
Time Frame: 21 days after last vaccination
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
Time Frame: 21 days after last vaccination
Total AGS-v specific immunoglobulin measured in serum 14 days after the first and/or second vaccination.
21 days after last vaccination

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
GM-CSF Cytokine Level as Measured by Luminex
Time Frame: 60 days after Day 42 Mosquito Feeding
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
60 days after Day 42 Mosquito Feeding
IL-10 Cytokine Level as Measured by Luminex
Time Frame: 60 days after Day 42 Mosquito Feeding
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
60 days after Day 42 Mosquito Feeding
IL-1B Cytokine Level as Measured by Luminex
Time Frame: 60 days after Day 42 Mosquito Feeding
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
60 days after Day 42 Mosquito Feeding
IL-2 Cytokine Level as Measured by Luminex
Time Frame: 60 days after Day 42 Mosquito Feeding
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
60 days after Day 42 Mosquito Feeding
IL-4 Cytokine Level as Measured by Luminex
Time Frame: 60 days after Day 42 Mosquito Feeding
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
60 days after Day 42 Mosquito Feeding
IL-5 Cytokine Level as Measured by Luminex
Time Frame: 60 days after Day 42 Mosquito Feeding
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
60 days after Day 42 Mosquito Feeding
Interferon-gamma Cytokine Level as Measured by Luminex
Time Frame: 60 days after Day 42 Mosquito Feeding
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
60 days after Day 42 Mosquito Feeding
Number of Adults Developed From 100 Eggs
Time Frame: Day 42 Mosquito feeding
Measurement of changes to Aedes aegypti mosquito life cycle post feeding on blood from participants after vaccination
Day 42 Mosquito feeding
Number of Eggs Laid
Time Frame: Day 42 Mosquito feeding
Measurement of changes to Aedes aegypti mosquito life cycle post feeding on blood from participants after vaccination
Day 42 Mosquito feeding
Number of Pupae Hatched of 100 Eggs
Time Frame: Day 42 Mosquito feeding
Measurement of changes to Aedes aegypti mosquito life cycle post feeding on blood from participants after vaccination
Day 42 Mosquito feeding
Percent of Eggs That Developed Into Pupae
Time Frame: Day 42 Mosquito feeding
Measurement of changes to Aedes aegypti mosquito life cycle post feeding on blood from participants after vaccination
Day 42 Mosquito feeding
Percent of Pupae That Developed Into Adults
Time Frame: Day 42 Mosquito feeding
Measurement of changes to Aedes aegypti mosquito life cycle post feeding on blood from participants after vaccination
Day 42 Mosquito feeding
TNF-a Cytokine Level as Measured by Luminex
Time Frame: 60 days after Day 42 Mosquito Feeding
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
60 days after Day 42 Mosquito Feeding
Total AGS-v Specific Immunoglobulin
Time Frame: 60 days after Day 42 Mosquito Feeding
Total AGS-v specific immunoglobulin measured in serum after the first and/or second vaccination.
60 days after Day 42 Mosquito Feeding

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2017

Primary Completion (Actual)

December 28, 2018

Study Completion (Actual)

December 28, 2018

Study Registration Dates

First Submitted

February 14, 2017

First Submitted That Met QC Criteria

February 14, 2017

First Posted (Actual)

February 16, 2017

Study Record Updates

Last Update Posted (Actual)

August 11, 2020

Last Update Submitted That Met QC Criteria

August 3, 2020

Last Verified

December 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 170059
  • 17-I-0059 (Other Identifier: NIAID)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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