Vector Borne DiseasesPhase 1NCT04350905
Characterization of Skin Immunity to Aedes Aegypti Saliva in Dengue-endemic Participants in Cambodia
A Phase 1 study testing Mosquito Feeding in people with Vector Borne Diseases, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Cambodia.
Trial summary
Background: Mosquito-borne viruses like dengue cause major illness and death worldwide, particularly in Southeast Asia. When mosquitoes deliver a virus into the skin of humans, they also leave saliva. Researchers want to learn more about skin immunity to mosquito saliva. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Vector Borne Diseases
- What is being tested?
- Mosquito Feeding
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteCambodia
- Study dates
- 27 Oct 2020to 9 Apr 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- -Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged 18 - 45 years
- Live within approximately 15 km of study site
- In good general health as evidenced by medical history
Show all 15Show fewer
- Willing to allow biological samples to be stored for future research.
- A female is eligible for this study if she meets 1 of the following:
- Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal
- ligation or are postmenopausal, as defined by no menses in >=1 year).
- --Of childbearing potential but has negative urine pregnancy test on Day 0
- Agrees to not use scented lotions, deodorants, or topical creams on each feeding day.
- Agrees to not take aspirin or any other NSAID (ex. ibuprofen) within 7 days of a biopsy.
- Agrees to not use oral or topical antihistamines or steroid creams or ointments throughout the
- study without prior permission of Principal Investigator (PI).
Who cannot join
- -Any underlying or current medical condition that, in the opinion of the investigator, would
- interfere with participation in the study.
- -History of severe allergic reaction (including to mosquito or other insect bites) with generalized
- urticaria, angioedema, anaphylaxis, anaphylactoid reaction or any other reaction described by
- the participant and deemed severe by the PI.
- Self-reported or known history of alcoholism or drug abuse within 6 months prior to enrollment
Show all 14Show fewer
- 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.
- -Any use of medications that affect blood clotting within 3 months or history of abnormal blood
- clotting
- -History of significant scarring such as keloids after previous biopsies, lacerations, abrasions,
- surgeries, or other skin procedures (e.g., cosmetic piercings) that are deemed by the PI to be a
- contraindication to protocol participation.
- -Pregnant or breastfeeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Characterization of Skin Immunity to Aedes Aegypti Saliva in Dengue-Endemic Participants in Cambodia
Background:
Mosquito-borne viruses like dengue cause major illness and death worldwide, particularly in Southeast Asia. When mosquitoes deliver a virus into the skin of humans, they also leave saliva. Researchers want to learn more about skin immunity to mosquito saliva. They hope this will help with future vaccines and treatments for these diseases.
Read more
Objective:
To compare the early and late innate immune response in the skin of Aedes aegypti bitten versus unbitten skin.
Eligibility:
Healthy people ages 18-45 who live within about 15 km of the study site in Chbar Mon
Design:
Participants will have 3 visits.
The baseline/screening visit will include:
Medical and medication history
Questions about participants demographic information, mosquito biting risk factors, and responses to mosquito or other insect bites
Physical exam
Urine sample for some participants
Mosquito feeding. A feeding device will be placed on the participant s arm for up to 20 minutes. The insects will feed through a mesh on the bottom of the feeding device. Participants may be given standard treatments for any skin reactions.
Blood tests
Four skin biopsies taken from bitten and unbitten skin. Local anesthetic will be administered, and a small tool will be used to remove the participant s skin.
Participants will have a second visit the next day. They will have a physical exam and blood tests. They will have 1 skin biopsy.
Participants will have a final visit about 2 weeks later. They will have a physical exam and blood tests.
During the study, participants will be asked to take measures to prevent more mosquito bites.
Read the detailed description
Mosquito-borne viruses continue to cause significant global morbidity and mortality, particularly in Southeast Asia. When mosquitoes deliver the virus into the skin of humans while probing for a blood meal, they deposit also saliva, which contains a myriad of pharmacologically active compounds that modulate the host immune system. Little is known about skin immunity to mosquito saliva, particularly in endemic volunteers as most clinical studies are performed in na(SqrRoot) ve individuals who have never or rarely been exposed to a particular mosquito vector. People living in endemic areas have had long-term repeated exposure to these vectors and therefore have different immune response to mosquito saliva, which could interfere with mosquito-borne disease vaccine effectiveness. Characterization of skin immunity via various technical modalities will be important in order to identify critical aspects of the innate and adaptive immune responses after a vector bite.
Here, we will execute a paired study of exposed-unexposed skin to carefully examine the innate and adaptive immune responses in the skin and blood to exposure of the saliva of Aedes aegypti, the mosquito vector of dengue, Zika, and chikungunya viruses. We will enroll 42 participants to undergo vector feeding and give blood samples at baseline and 2 and 14 days later. Additionally, participants will give skin punch biopsy samples of bitten (exposed) and unbitten (unexposed) skin. For analysis, we will group 10-12 participants in each of 4 technical modality cohorts or groups : 1) immunohistochemistry, 2) RNA sequencing, 3) flow cytometry, and 4) T-cell receptor sequencing. With the current rise of vector-borne diseases in the United States and around the world, we hope the results of this study contribute to future vaccine design and clinical development strategies for vector#borne diseases.
- Conditions
- Vector Borne Diseases
- Being tested
- Mosquito Feeding
- Keywords
- Vector-Borne Diseases, Immune Response, Mosquito Feeding, Arbovirus, Southeast Asia
- Medical subject headings
- Vector Borne Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mosquito FeedingOther
Mosquito feedings will be conducted with Aedes aegypti colonies raised at the CNM (National Malaria Center) Malaria and Vector Research Laboratory (MVRL), an established state of the art insectaries for mosquitoes was built in 2014 to ACL2 (arthropodcontainment level 2)-level specifications.
| Study group | Role | What they receive |
|---|---|---|
| Mosquito Feeding | Experimental | Each participant will receive one mosquito feeding with 5 starved female Aedes aegypti mosquitoes. Receives: Other: Mosquito Feeding |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of Change in Early and Late Innate Immune Responses Using Gene Expression and Flow Cytometry in Participants' Skin
Measurement of changes in the early and late innate immune response and cellular recruitment in bitten skin versus unbitten skin by: a) immunohistochemistry of target proteins at Day 0 timepoints b) immunophenotyping of innate immune cell subsets in dissociated skin sample at Day 0 timepoints c) determination of cytokine profile in dissociated skin sample supernatant at Day 0 timepoints d) differential cDNA expression prepared from skin RNA and analyzed via RNASeq at Day 0 timepoints
Measured: Day 0 timepoints
Measurement of Changes in the Adaptive Immune Response and Cellular Recruitment in the Skin of Bitten Versus Unbitten Skin After Sixth and Final Feeding in Each Vector Group.
Measurement of changes in the adaptive immune response and cellular recruitment in bitten skin versus unbitten skin by: a) immunohistochemistry of target proteins at Day 2 timepoints b) phenotyping of adaptive immune cell subsets in dissociated skin sample at Day 2 timepoints c) determination of cytokine profile in dissociated skin sample supernatant at Day 2 timepoints d) differential cDNA expression prepared from skin RNA and analyzed via RNASeq at Day 2 timepoints
Measured: Day 2 (48 hr post feeding)
Secondary outcomes (1)
Flow Cytometry Analysis of PBMCs Collected Day 0 (Baseline) and Days 2 and 14 After Feeding for Saliva-specific T-cells
Describing and understanding cellular immunity to Aedes saliva in heavily exposed individuals will simulate endemic conditions and will inform vaccine design in these target populations.
Measured: Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2020
- Study start27 Oct 2020
- Primary completion9 Apr 2021
- Study completion9 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Vector Borne DiseasesStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Participants were all exposed to 5 uninfected Aedes aegypti mosquitos on their forearm. Biopsies were taken of bitten and unbitten skin.
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jessica E Manning, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04350905
- Sponsor's protocol ID
- 999920053
- Other IDs
- 20-I-N053
- Status last verified
- 9 Apr 2021
- First submitted
- 16 Apr 2020
- Last updated
- 12 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Durnez L, Mao S, Denis L, Roelants P, Sochantha T, Coosemans M. Outdoor malaria transmission in forested villages of Cambodia. Malar J. 2013 Sep 17;12:329. doi: 10.1186/1475-2875-12-329.
PubMed 24044424Manning JE, Morens DM, Kamhawi S, Valenzuela JG, Memoli M. Mosquito Saliva: The Hope for a Universal Arbovirus Vaccine? J Infect Dis. 2018 Jun 5;218(1):7-15. doi: 10.1093/infdis/jiy179.
PubMed 29617849Huy R, Buchy P, Conan A, Ngan C, Ong S, Ali R, Duong V, Yit S, Ung S, Te V, Chroeung N, Pheaktra NC, Uok V, Vong S. National dengue surveillance in Cambodia 1980-2008: epidemiological and virological trends and the impact of vector control. Bull World Health Organ. 2010 Sep 1;88(9):650-7. doi: 10.2471/BLT.09.073908. Epub 2010 Apr 7.
PubMed 20865069
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Skin Immunity to Aedes Aegypti Saliva in Dengue-Endemic Participants in Cambodia
- ClinicalTrials.gov ID
- NCT04350905
- Acronym / sponsor ID
- 999920053
- Conditions
- Vector Borne Diseases
- Keywords
- Vector-Borne Diseases, Immune Response, Mosquito Feeding, Arbovirus, Southeast Asia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 27 Oct 2020 (actual)
- Primary completion
- 9 Apr 2021 (actual)
- Study completion
- 9 Apr 2021 (actual)
- First posted
- 17 Apr 2020 (actual)
- Results
- Posted 12 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Mosquito-borne viruses like dengue cause major illness and death worldwide, particularly in Southeast Asia. When mosquitoes deliver a virus into the skin of humans, they also leave saliva. Researchers want to learn more about skin immunity to mosquito saliva. They hope this will help with future vaccines and treatments for these diseases.
Objective:
To compare the early and late innate immune response in the skin of Aedes aegypti bitten versus unbitten skin.
Eligibility:
Healthy people ages 18-45 who live within about 15 km of the study site in Chbar Mon
Design:
Participants will have 3 visits.
The baseline/screening visit will include:
Medical and medication history
Questions about participants demographic information, mosquito biting risk factors, and responses to mosquito or other insect bites
Physical exam
Urine sample for some participants
Mosquito feeding. A feeding device will be placed on the participant s arm for up to 20 minutes. The insects will feed through a mesh on the bottom of the feeding device. Participants may be given standard treatments for any skin reactions.
Blood tests
Four skin biopsies taken from bitten and unbitten skin. Local anesthetic will be administered, and a small tool will be used to remove the participant s skin.
Participants will have a second visit the next day. They will have a physical exam and blood tests. They will have 1 skin biopsy.
Participants will have a final visit about 2 weeks later. They will have a physical exam and blood tests.
During the study, participants will be asked to take measures to prevent more mosquito bites.
Detailed description
Mosquito-borne viruses continue to cause significant global morbidity and mortality, particularly in Southeast Asia. When mosquitoes deliver the virus into the skin of humans while probing for a blood meal, they deposit also saliva, which contains a myriad of pharmacologically active compounds that modulate the host immune system. Little is known about skin immunity to mosquito saliva, particularly in endemic volunteers as most clinical studies are performed in na(SqrRoot) ve individuals who have never or rarely been exposed to a particular mosquito vector. People living in endemic areas have had long-term repeated exposure to these vectors and therefore have different immune response to mosquito saliva, which could interfere with mosquito-borne disease vaccine effectiveness. Characterization of skin immunity via various technical modalities will be important in order to identify critical aspects of the innate and adaptive immune responses after a vector bite.
Here, we will execute a paired study of exposed-unexposed skin to carefully examine the innate and adaptive immune responses in the skin and blood to exposure of the saliva of Aedes aegypti, the mosquito vector of dengue, Zika, and chikungunya viruses. We will enroll 42 participants to undergo vector feeding and give blood samples at baseline and 2 and 14 days later. Additionally, participants will give skin punch biopsy samples of bitten (exposed) and unbitten (unexposed) skin. For analysis, we will group 10-12 participants in each of 4 technical modality cohorts or groups : 1) immunohistochemistry, 2) RNA sequencing, 3) flow cytometry, and 4) T-cell receptor sequencing. With the current rise of vector-borne diseases in the United States and around the world, we hope the results of this study contribute to future vaccine design and clinical development strategies for vector#borne diseases.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Participants were all exposed to 5 uninfected Aedes aegypti mosquitos on their forearm. Biopsies were taken of bitten and unbitten skin.
| Arm | Type | Receives |
|---|---|---|
| Mosquito Feeding | Experimental | Other: Mosquito FeedingEach participant will receive one mosquito feeding with 5 starved female Aedes aegypti mosquitoes. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- -Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged 18 - 45 years
- Live within approximately 15 km of study site
Key exclusion criteria (14 listed)
- -Any underlying or current medical condition that, in the opinion of the investigator, would
- interfere with participation in the study.
- -History of severe allergic reaction (including to mosquito or other insect bites) with generalized
- urticaria, angioedema, anaphylaxis, anaphylactoid reaction or any other reaction described by
- the participant and deemed severe by the PI.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mosquito FeedingMosquito feedings will be conducted with Aedes aegypti colonies raised at the CNM (National Malaria Center) Malaria and Vector Research Laboratory (MVRL), an established state of the art insectaries for mosquitoes was built in 2014 to ACL2 (arthropodcontainment level 2)-level specifications. | Other | Mosquito Feeding |
Primary outcome
Measurement of Change in Early and Late Innate Immune Responses Using Gene Expression and Flow Cytometry in Participants' Skin
Time frame: Day 0 timepoints
Measurement of changes in the early and late innate immune response and cellular recruitment in bitten skin versus unbitten skin by: a) immunohistochemistry of target proteins at Day 0 timepoints b) immunophenotyping of innate immune cell subsets in dissociated skin sample at Day 0 timepoints c) determination of cytokine profile in dissociated skin sample supernatant at Day 0 timepoints d) differential cDNA expression prepared from skin RNA and analyzed via RNASeq at Day 0 timepoints
Measurement of Changes in the Adaptive Immune Response and Cellular Recruitment in the Skin of Bitten Versus Unbitten Skin After Sixth and Final Feeding in Each Vector Group.
Time frame: Day 2 (48 hr post feeding)
Measurement of changes in the adaptive immune response and cellular recruitment in bitten skin versus unbitten skin by: a) immunohistochemistry of target proteins at Day 2 timepoints b) phenotyping of adaptive immune cell subsets in dissociated skin sample at Day 2 timepoints c) determination of cytokine profile in dissociated skin sample supernatant at Day 2 timepoints d) differential cDNA expression prepared from skin RNA and analyzed via RNASeq at Day 2 timepoints
1 secondary outcome
Flow Cytometry Analysis of PBMCs Collected Day 0 (Baseline) and Days 2 and 14 After Feeding for Saliva-specific T-cells
Time frame: Day 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24044424Durnez L, Mao S, Denis L, Roelants P, Sochantha T, Coosemans M. Outdoor malaria transmission in forested villages of Cambodia. Malar J. 2013 Sep 17;12:329. doi: 10.1186/1475-2875-12-329.
- Background: PubMed 29617849Manning JE, Morens DM, Kamhawi S, Valenzuela JG, Memoli M. Mosquito Saliva: The Hope for a Universal Arbovirus Vaccine? J Infect Dis. 2018 Jun 5;218(1):7-15. doi: 10.1093/infdis/jiy179.
- Background: PubMed 20865069Huy R, Buchy P, Conan A, Ngan C, Ong S, Ali R, Duong V, Yit S, Ung S, Te V, Chroeung N, Pheaktra NC, Uok V, Vong S. National dengue surveillance in Cambodia 1980-2008: epidemiological and virological trends and the impact of vector control. Bull World Health Organ. 2010 Sep 1;88(9):650-7. doi: 10.2471/BLT.09.073908. Epub 2010 Apr 7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jessica E Manning, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mosquito Feeding in people with Vector Borne Diseases, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Cambodia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Cambodia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of Change in Early and Late Innate Immune Responses Using Gene Expression and Flow Cytometry in Participants' Skin (time frame: Day 0 timepoints). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04350905, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2022; AzTrials last refreshed its copy on 8 Nov 2026.