Characterizing Humoral Immune Response to Mosquito Bites

NCT04478370 | Completed

• 1 other identifier: MAL19009
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 1

Brief Summary

The characteristics of the humoral response directed against mosquito saliva antigens are not known precisely. This is a major limitation for using immunological markers as an outcome in epidemiological trials and as an indicator for operational deployment of interventions. Recent advances in the assembly of the genome of some Anopheles and Aedes mosquito vector species has facilitated the identification of new candidate peptides in silico, using the sequences of orthologous salivary gland proteins and B-cell prediction algorithms. The objective of this study is to assess the humoral immune response directed against candidate peptides following controlled exposure to laboratory-adapted colonies of An. minimus, An. maculatus and An. dirus, Ae. aegypti and Ae. albopictus. This research will provide essential information to identify and validate immunological markers of human exposure to malaria and dengue mosquito vectors in Southeast Asia. Immunological markers would be useful to understand transmission dynamics and predict the risk of transmission as part of a surveillance system, and to assess the efficacy of vector-control interventions in entomological trials or during operational deployment of interventions in the region.

Conditions

Dengue; Malaria

Keywords

Mosquito bites; Biomarkers; Malaria vectors; Dengue vectors

Outcome Measures

Primary Outcomes (3)

• Levels of specific antibody titers against candidate peptides before and during repeated exposure to laboratory-reared mosquito bites determined by ELISA and mesoscale screening.

  baseline through day 112

• Kinetics of specific antibody titers against candidate peptides before and during repeated exposure to laboratory-reared mosquito bites determined by ELISA and mesoscale screening.

  baseline through day 112

• Sequence of saliva antigens determined with an immuno-proteomic method (2D gel electrophoresis of salivary gland protein extracts, Western blot and mass spectrometry).

  Day 14 through day 112

Secondary Outcomes (2)

• Comparison of the antibody titers determined in subgroups corresponding to different level of exposure.

  Day 0, 7 (baseline), 14, 21, 28, 35, 42, 49, 56 (exposure period), 63, 70, 77, 84, 91, 98, 105 and 112 (post-exposure period).

• Comparison of the antibody titers determined in DBS and venous blood samples.

  Day 0, 7 (baseline), 14, 21, 28, 35, 42, 49, 56 (exposure period), 63, 70, 77, 84, 91, 98, 105 and 112 (post-exposure period).

Study Arms (5)

An. minimus

EXPERIMENTAL

This arm will be divided into 2 groups; the low-exposure groups and the high-exposure group. In the low-exposure group, participants will be exposed to 5 mosquito bites at weekly intervals from day 14 to day 56 (seven challenges with 5 mosquito bites/challenge over six weeks, yielding a total of 35 mosquito bites). In the high-exposure group, participants will be exposed to 5 mosquito bites on day 14 and then to 50 mosquito bites at weekly intervals from day 21 to day 56 (one challenge with 5 mosquito bites and six challenges with 50 mosquito bites/challenge over 6 weeks, yielding a total of 305 mosquito bites).

Biological: Mosquito bites

An. maculatus

EXPERIMENTAL

Same as above

Biological: Mosquito bites

An. dirus

EXPERIMENTAL

Same as above

Biological: Mosquito bites

Ae. aegypti

EXPERIMENTAL

Same as above

Biological: Mosquito bites

Ae. albopictus

EXPERIMENTAL

Same as above

Biological: Mosquito bites

Interventions

Mosquito bites BIOLOGICAL

Participants will be exposed to mosquito bites. For the low-dose challenge, five 5 to 7-day-old nulliparous female imagoes (i.e. that have never blood fed before) will be introduced individual into 50 mL plastic tube covered with netting material. For high-dose challenge, 47 mosquitoes will be split into four plastic cups of 10 cm in diameter covered with netting material (three cups with 12 mosquitoes and one cup with 11 mosquitoes), and 3 mosquitoes will be introduced individually into 50 mL plastic tubes. Mosquito bites administered on participant's arm will be used to assess immediate and delayed skin reactions. Immediate and delayed skin reactions will be recorded respectively 20-30 min and 24-36 hours after the day 14 and day 21 challenges, requiring additional visits at day 15 and 22.

Ae. aegypti; Ae. albopictus; An. dirus; An. maculatus; An. minimus

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female participant judged by a responsible physician with no abnormality identified on a medical evaluation;
• Thai, Burmese or Karen ethnicity;
• Aged ≥ 18 to \<60 years old;
• Living in Mae Sot city for the last 12 months;
• Willing to participate in the activity and able to give informed consent for participating in the study;
• Able to tolerate direct mosquito exposure.

You may not qualify if:

• History of travel in a malaria endemic are (rural village) in the last 12 months, or plan to do so during the study;
• Medication or condition deemed to interfere with the outcome measure by a responsible physician;
• Moderate and severe anemia (haemoglobin concentration less than 110 g/L of blood);
• Hypersensitivity or anaphylaxis to mosquito bites;
• Pregnant women

Sponsors & Collaborators

• Burnet Institute: collaborator
• Agency for Science, Technology and Research: collaborator
• University of Oxford: lead
• National Health and Medical Research Council, Australia: collaborator

Study Sites (1)

Shoklo Malaria Research unit (SMRU)

Mae Sot, Changwat Tak, 63110, Thailand

Location

Related Publications (2)

• Sawasdichai S, Chaumeau V, Kearney E, Wasisakun P, Simpson JA, Price DJ, Chotirat S, Renia L, Bergmann-Leitner E, Fowkes F, Nosten F. Characterizing antibody responses to mosquito salivary antigens of the Southeast Asian vectors of malaria and dengue with a human challenge model of controlled exposure: a protocol. Wellcome Open Res. 2023 Jul 11;8:135. doi: 10.12688/wellcomeopenres.19049.2. eCollection 2023.

  PMID: 37456919 RESULT

• Chaumeau V, Kearney EA, Wasisakun P, Sawasdichai S, Aung AA, Agius PA, Min TH, da Silva Goncalves D, O'Flaherty K, Rouers A, Aryalamloed S, Htoo GN, Sue MP, Tha NM, Chanida N, Gornsawun G, Chotirat S, Simpson JA, Renia L, Nosten F, Fowkes FJI. Assessment of antibody responses to Anopheles SG6-P1 and Aedes N-term 34 kDa salivary peptides: a randomised human-challenge trial of controlled exposures to vector bites. BMC Med. 2026 Mar 2. doi: 10.1186/s12916-026-04732-z. Online ahead of print.

  PMID: 41765941 DERIVED

MeSH Terms

Conditions

Malaria; Dengue

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Study Officials

• François Nosten

  Shoklo Malaria Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a human challenge model with five arms corresponding to controlled exposure to bites of uninfected laboratory-adapted colonies of Anopheles minimus, An. maculatus, An. dirus, Aedes. aegypti or Ae. albopictus.

Study Record Dates

• First Submitted: June 29, 2020
• First Posted: July 20, 2020
• Study Start: January 21, 2021
• Primary Completion: July 23, 2025
• Study Completion: July 23, 2025
• Last Updated: February 3, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)