Chikungunya, Dengue, Leishmaniasis, Malaria, Zika
Conditions
Keywords
Mosquito, Saliva, Immune Response, Sand Fly, Biopsy
Brief summary
Background: Mosquitoes and similar insects called sand flies carry parasites that can cause diseases. These viruses and parasites can spread quickly and be difficult to control. How people s bodies respond to insect bites may affect how they get infected. The response to bites is caused by the immune system, which helps fight off infections. Researchers want to study the immune response in skin to mosquito or sand fly bites and how the response changes after bites on multiple days. This may help researchers develop better vaccines. Objective: To study the immune response in skin to certain insect bites and how that changes after bites on multiple days. Eligibility: Healthy adults ages 18-64 Design: Participants will be screened under another protocol. Women must agree to practice effective contraception or abstinence. All participants must agree to not donate blood or use certain lotions or creams on visit days. Some participants will have 2 visits over a week. Others will have 5 visits over 8 weeks. All participants will have the following at least once: Medical history Physical exam Blood and urine collected Mosquito or sand fly feeding. Up to 10 insects will feed on participant s arm for up to 20 minutes. The insects are grown at NIH and do not carry any diseases. The skin will be checked and bites will be treated. Skin samples taken. The skin will be cleaned and numbed. A tool will remove a small piece of skin from 3 places on the arm. About a week after the last visit, participants will be called to see how they feel.
Detailed description
Vector-borne diseases continue to cause significant morbidity and mortality worldwide despite ongoing control efforts. Vectors like sand flies and mosquitoes deliver the pathogen into the skin of humans while taking a blood meal. Most vaccines under development ignore the importance of the complex infectious inoculum delivered by the vector and the local immune response that occurs at the site of the bite. In addition, many preclinical studies are carried out in animal models that do not replicate the natural route of infection, transmission by vector bites, and often bypass the skin interface altogether. As such, these studies do not evaluate what role the vector plays in the initiation of these infections. Further compounding this problem, many clinical studies are performed in naïve individuals who have never been exposed to the vector, while those living in endemic areas will have had long-term exposure to vectors through uninfected bites. A cumulative body of evidence from animal models demonstrates that a variety of vector-derived components are co-delivered with the pathogen and may play an important role in the establishment of infection. There is limited knowledge of the effect of these vector-derived factors on the immune response in human skin and their potential impact on infection establishment. In this protocol, we will examine the early skin immune response to bites of three arthropods: the mosquito Aedes aegypti, the vector of Zika, dengue, and chikungunya viruses; the mosquito Anopheles gambiae, the vector of malaria; and the sand fly Lutzomyia longipalpis, the vector of leishmaniasis. We will also explore how multiple vector bite exposures over time modulate future immune response at the bite site. Healthy participants will come to the National Institutes of Health (NIH) and undergo feeding by one of the three vectors, then have three skin punch biopsies performed by trained medical practitioners to evaluate local immune response. Participants in Cohort A will have one feeding; participants in Cohort B will have 4 feedings, each 2 weeks apart. Biopsies will be collected after the final feeding. Blood will be collected after the one feeding in Cohort A and after the fourth and final feeding in Cohort B to assess systemic immune response. 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.
Interventions
OTHEROne vector feeding
Participants will undergo one feeding by one of three colony- reared vectors (Aedes aegypti mosquitos, Anopheles gambiae mosquitos, or Lutzomyia longipalpis sand flies)
OTHERFour vector feeding
Participants will undergo four feedings by one of three colony- reared vectors (Aedes aegypti mosquitos, Anopheles gambiae mosquitos, or Lutzomyia longipalpis sand flies), each about 2 weeks apart, with the same vector type.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* INCLUSION CRITERIA: Individuals must meet all of the following criteria to be eligible for study participation: * Healthy women and men who are greater than or equal to 18 and less than or equal to 64 years of age. * Able to provide informed consent. * Willingness to complete all study visits and comply with all study requirements. * Willing to have samples 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 greater than or equal to 1 year). * Of childbearing potential but agrees to practice effective contraception or abstinence for 4 weeks prior to enrollment through the completion of the study. 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 that is used by the female: 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. * Agrees to not use scented lotions, deodorants, or topical creams on each feeding day. * Agrees to not take aspirin or any other NSAID within 7 days of a biopsy. * Agrees to not use topical steroid creams or ointments throughout the study without prior permission of Principal Investigator (PI). * Vector-specific antibody enzyme-linked immunosorbent assay (ELISA) to one of the three vectors (the one to which the individual is assigned) is \<2.5 standard deviations above the negative control for Cohort A only.
Exclusion criteria
Individuals meeting any of the following criteria will be excluded from study participation: * Any underlying or current medical condition that, in the opinion of the investigator, would interfere with participation in the study. * Any participant that is HIV positive. * A clinically significant (as determined by the PI) baseline Grade 1 or greater toxicity by the toxicity table. * History of severe allergic reaction (including to mosquito or other insect bites) with generalized urticaria, angioedema, anaphylaxis, or anaphylactoid reaction. * Prone to allergic responses and/or significant history of allergies, including seasonal or specific allergies as determined by the PI. * Receipt of any investigational drug that is unlicensed 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 test for drugs of abuse at screening (excluding positive test for tetrahydrocannabinol (THC) or its metabolites if usage is less than 3 times per week). * 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, history of abnormal blood clotting, or result outside of the normal laboratory range for measurements of prothrombin time (PT), partial thromboplastin time (PTT), or international normalized ratio (INR) that may suggest a problem with blood clotting. * History of significant scarring 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. Co-enrollment Guidelines: Co-enrollment in other trials is restricted, but may take place after consultation with the study staff and approval from the PI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | Up to 48 hours post bite | Number of differentially expressed genes between bitten and unbitten skin with adjusted p-values (adjusted for multiple comparisons) of \< 0.05 and a minimum absolute fold change \> 4 in samples derived from skin biopsies for the three vector groups - Aedes aegypti, Anopheles gambiae, Lutzomyia longipalpis |
| Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Up to 48 hours post bite | Number of participants with certain types of inflammatory cell infiltrates, which includes neutrophils, mononuclear cells, and eosinophils, in the skin biopsies of bitten skin at 30 minutes, 4 hours, and 48 hours post bite for each of the three vector groups - Aedes aegypti, Anopheles gambiae, and Lutzomyia longipalpis |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Exposure Cohort A: Aedes Aegypti One vector feeding: Participants will undergo one feeding by Aedes aegypti mosquitoes and then three biopsies on Day 0 were performed | 15 |
| Multiple Exposure Cohort B: Aedes Aegypti Four vector feeding: Participants will undergo four feedings by Aedes aegypti mosquitos each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding | 15 |
| Single Exposure Cohort A: Anopheles Gambiae One vector feeding: Participants will undergo one feeding by Anopheles gambiae mosquitoes and then three biopsies on Day 0 were performed | 15 |
| Multiple Exposure Cohort B: Anopheles Gambiae Four vector feeding: Participants will undergo four feedings by Anopheles gambiae mosquitoes each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding | 14 |
| Single Exposure Cohort A: Lutzomyia Longipalpis One vector feeding: Participants will undergo one feeding by Lutzomyia longipalpis and then three biopsies on Day 0 were performed | 15 |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis Four vector feeding: Participants will undergo four feedings by Lutzomyia longipalpis each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding | 15 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Single Exposure Cohort A: Aedes Aegypti | Total | Multiple Exposure Cohort B: Lutzomyia Longipalpis | Single Exposure Cohort A: Lutzomyia Longipalpis | Multiple Exposure Cohort B: Anopheles Gambiae | Single Exposure Cohort A: Anopheles Gambiae | Multiple Exposure Cohort B: Aedes Aegypti |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 31.27 years STANDARD_DEVIATION 8.36 | 32.62 years STANDARD_DEVIATION 9.89 | 32.73 years STANDARD_DEVIATION 11.44 | 32.47 years STANDARD_DEVIATION 11.62 | 33.07 years STANDARD_DEVIATION 9.42 | 35.60 years STANDARD_DEVIATION 9.66 | 30.67 years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 15 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 72 Participants | 11 Participants | 11 Participants | 12 Participants | 12 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 6 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 19 Participants | 4 Participants | 4 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 9 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 5 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 49 Participants | 9 Participants | 7 Participants | 8 Participants | 10 Participants | 7 Participants |
| Region of Enrollment United States | 15 participants | 89 participants | 15 participants | 15 participants | 14 participants | 15 participants | 15 participants |
| Sex: Female, Male Female | 6 Participants | 57 Participants | 11 Participants | 11 Participants | 8 Participants | 9 Participants | 12 Participants |
| Sex: Female, Male Male | 9 Participants | 32 Participants | 4 Participants | 4 Participants | 6 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 14 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 1 / 15 | 5 / 15 | 3 / 15 | 6 / 14 | 1 / 15 | 6 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 14 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups
Number of differentially expressed genes between bitten and unbitten skin with adjusted p-values (adjusted for multiple comparisons) of \< 0.05 and a minimum absolute fold change \> 4 in samples derived from skin biopsies for the three vector groups - Aedes aegypti, Anopheles gambiae, Lutzomyia longipalpis
Time frame: Up to 48 hours post bite
Population: Every participant who had skin biopsies.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single Exposure Cohort A: Aedes Aegypti | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 4 hours post bite | 227 number of differentially expressed genes |
| Single Exposure Cohort A: Aedes Aegypti | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 30 minutes post bite | 18 number of differentially expressed genes |
| Single Exposure Cohort A: Aedes Aegypti | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 48 hours post bite | NA number of differentially expressed genes |
| Multiple Exposure Cohort B: Aedes Aegypti | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 4 hours post bite | 179 number of differentially expressed genes |
| Multiple Exposure Cohort B: Aedes Aegypti | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 30 minutes post bite | NA number of differentially expressed genes |
| Multiple Exposure Cohort B: Aedes Aegypti | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 48 hours post bite | 503 number of differentially expressed genes |
| Single Exposure Cohort A: Anopheles Gambiae | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 4 hours post bite | 12 number of differentially expressed genes |
| Single Exposure Cohort A: Anopheles Gambiae | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 30 minutes post bite | 1 number of differentially expressed genes |
| Single Exposure Cohort A: Anopheles Gambiae | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 48 hours post bite | NA number of differentially expressed genes |
| Multiple Exposure Cohort B: Anopheles Gambiae | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 4 hours post bite | 72 number of differentially expressed genes |
| Multiple Exposure Cohort B: Anopheles Gambiae | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 30 minutes post bite | NA number of differentially expressed genes |
| Multiple Exposure Cohort B: Anopheles Gambiae | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 48 hours post bite | 982 number of differentially expressed genes |
| Single Exposure Cohort A: Lutzomyia Longipalpis | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 4 hours post bite | 172 number of differentially expressed genes |
| Single Exposure Cohort A: Lutzomyia Longipalpis | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 30 minutes post bite | 5 number of differentially expressed genes |
| Single Exposure Cohort A: Lutzomyia Longipalpis | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 48 hours post bite | NA number of differentially expressed genes |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 30 minutes post bite | NA number of differentially expressed genes |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 48 hours post bite | 797 number of differentially expressed genes |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis | Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups | 4 hours post bite | 204 number of differentially expressed genes |
Primary
Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups
Number of participants with certain types of inflammatory cell infiltrates, which includes neutrophils, mononuclear cells, and eosinophils, in the skin biopsies of bitten skin at 30 minutes, 4 hours, and 48 hours post bite for each of the three vector groups - Aedes aegypti, Anopheles gambiae, and Lutzomyia longipalpis
Time frame: Up to 48 hours post bite
Population: Every participant who had skin biopsies.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single Exposure Cohort A: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 48 hours post bite | NA participants |
| Single Exposure Cohort A: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 48 hours post bite | NA participants |
| Single Exposure Cohort A: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 30 minutes post bite | 4 participants |
| Single Exposure Cohort A: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 4 hours post bite | 3 participants |
| Single Exposure Cohort A: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 48 hours post bite | NA participants |
| Single Exposure Cohort A: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 4 hours post bite | 5 participants |
| Single Exposure Cohort A: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 30 minutes post bite | 3 participants |
| Single Exposure Cohort A: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 30 minutes post bite | 3 participants |
| Single Exposure Cohort A: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 4 hours post bite | 5 participants |
| Multiple Exposure Cohort B: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 48 hours post bite | 4 participants |
| Multiple Exposure Cohort B: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 4 hours post bite | 5 participants |
| Multiple Exposure Cohort B: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 30 minutes post bite | NA participants |
| Multiple Exposure Cohort B: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 30 minutes post bite | NA participants |
| Multiple Exposure Cohort B: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 30 minutes post bite | NA participants |
| Multiple Exposure Cohort B: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 48 hours post bite | 8 participants |
| Multiple Exposure Cohort B: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 4 hours post bite | 6 participants |
| Multiple Exposure Cohort B: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 48 hours post bite | 1 participants |
| Multiple Exposure Cohort B: Aedes Aegypti | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 4 hours post bite | 3 participants |
| Single Exposure Cohort A: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 30 minutes post bite | 1 participants |
| Single Exposure Cohort A: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 4 hours post bite | 0 participants |
| Single Exposure Cohort A: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 4 hours post bite | 1 participants |
| Single Exposure Cohort A: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 48 hours post bite | NA participants |
| Single Exposure Cohort A: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 48 hours post bite | NA participants |
| Single Exposure Cohort A: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 30 minutes post bite | 0 participants |
| Single Exposure Cohort A: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 48 hours post bite | NA participants |
| Single Exposure Cohort A: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 4 hours post bite | 0 participants |
| Single Exposure Cohort A: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 30 minutes post bite | 2 participants |
| Multiple Exposure Cohort B: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 4 hours post bite | 2 participants |
| Multiple Exposure Cohort B: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 30 minutes post bite | NA participants |
| Multiple Exposure Cohort B: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 30 minutes post bite | NA participants |
| Multiple Exposure Cohort B: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 30 minutes post bite | NA participants |
| Multiple Exposure Cohort B: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 4 hours post bite | 3 participants |
| Multiple Exposure Cohort B: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 4 hours post bite | 2 participants |
| Multiple Exposure Cohort B: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 48 hours post bite | 0 participants |
| Multiple Exposure Cohort B: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 48 hours post bite | 7 participants |
| Multiple Exposure Cohort B: Anopheles Gambiae | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 48 hours post bite | 1 participants |
| Single Exposure Cohort A: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 4 hours post bite | 2 participants |
| Single Exposure Cohort A: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 4 hours post bite | 3 participants |
| Single Exposure Cohort A: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 48 hours post bite | NA participants |
| Single Exposure Cohort A: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 30 minutes post bite | 0 participants |
| Single Exposure Cohort A: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 48 hours post bite | NA participants |
| Single Exposure Cohort A: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 48 hours post bite | NA participants |
| Single Exposure Cohort A: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 30 minutes post bite | 3 participants |
| Single Exposure Cohort A: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 30 minutes post bite | 0 participants |
| Single Exposure Cohort A: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 4 hours post bite | 1 participants |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 30 minutes post bite | NA participants |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 4 hours post bite | 3 participants |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 4 hours post bite | 4 participants |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 48 hours post bite | 2 participants |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 48 hours post bite | 8 participants |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Neutrophils 48 hours post bite | 0 participants |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Eosinophils 30 minutes post bite | NA participants |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 4 hours post bite | 6 participants |
| Multiple Exposure Cohort B: Lutzomyia Longipalpis | Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups | Mononuclear Cells 30 minutes post bite | NA participants |