Inclusion Criteria:
1. Male or female between 18 and 55 years of age, inclusive, at the time of screening.
2. Able and willing to comply with all research requirements, in the opinion of the investigator.
3. Good general health as determined by physical examination, laboratory screening, and review of medical history.
4. Available for the duration of the study, which is approximately 50 weeks.
5. Willingness to participate in the study as evidenced by signing the informed consent document.
6. Participant has 12-lead electrocardiogram (ECG\*) and clinical laboratory evaluations at screening with no clinically significant abnormalities, as assessed by the investigator. \*A normal ECG is defined as the presence of normal sinus rhythm (heart rate 45-100 beats per minute \[bpm\], inclusive) and the absence of:
1. QT interval corrected by Fridericia (QTcF) \>450 milliseconds (ms) in male participants or \>460 ms in female participants;
2. PR interval \>220 ms;
3. QRS duration ≧ 110ms;
4. Complete left or right bundle branch block;
5. 2nd or 3rd degree atrioventricular block;
6. Sustained ventricular or atrial arrhythmia;
7. ST elevation consistent with cardiac ischemia;
8. Ventricular or atrial premature contractions in couplets or higher order groupings.
7. Females only: Female participants must meet one of the following two (2) criteria:
1. No reproductive potential due to post-menopausal status (12 months of natural) \[spontaneous\] amenorrhea or surgical procedure such as hysterectomy, bilateral oophorectomy, bilateral salpingectomy, tubal coil/Essure or tubal ligation, females in a monogamous relationship with a vasectomized male partner or females who exclusively have sex with female partners.
2. Female participants of childbearing potential agree to practice highly effective contraception before enrollment and through 60 days post-DENV-3 challenge using one of the following methods: condoms (male or female) with spermicide; diaphragm, or cervical cap with spermicide; intrauterine device; contraceptive pills, patch, injection, intravaginal ring or other FDA-approved contraceptive method; male partner has previously undergone a vasectomy; abstinence (\> 6 months since last sexual encounter). Vasectomized partner is a highly effective contraceptive method provided that the partner is the sole sexual partner of the person of childbearing potential and the absence of sperm has been confirmed. If not, additional highly effective method(s) of contraception should be used.
8. Male participants are encouraged but not required to practice highly effective contraception to avoid pregnancy in their partner from 30 days prior to enrollment through 60 days post-DENV-3 challenge.
9. Females of childbearing potential must agree to not donate ova or oocytes during the study. Males must refrain from sperm donation during the study
10. Have an available phone running iOS 15.0 or later or Android phone running software v7.0 or higher, willing to download the myMedidata app, and willing to complete daily electronic diaries when required.
Exclusion Criteria:
1. Females only: Currently pregnant, as determined by positive beta-human choriogonadotropin (beta-HCG) test, or breast-feeding.
2. The participant has a history of significant alcoholism or drug/chemical abuse within 12 months prior to enrollment that has caused medical, occupational, or family problems as indicated by participant history.
3. Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a participant's ability to give informed consent.
4. A participant with a confirmed screening laboratory value of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), or serum creatinine. Values of Grade 1 or above for these tests may be repeated to confirm a Grade 1 or above value. Abnormal laboratory values other than those specified will not be exclusionary if the clinician deems them not clinically significant.
5. Any other significant disease, disorder or finding which may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study or impair interpretation of the study data, in the judgment of the Investigator.
6. Asplenia (absence of normal spleen function).
7. History of confirmed or suspected immunodeficiency.
8. Asthma that is unstable requiring emergent care, urgent care, hospitalization or intubation during the past 6 months.
9. Diabetes mellitus (type I or II) currently requiring medication for control.
10. Hypertension that is not well controlled by medication prior to enrollment. Two repeat measurements are allowed more than 10 minutes apart in the absence of any other concerning health screening issues.
11. Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with intramuscular injections or blood draws.
12. History of chronic or active neurologic diseases including seizure disorder and chronic migraine headaches. Exceptions are: i) childhood febrile seizures, or ii) seizures secondary to alcohol withdrawal more than three \[3\] years ago.
13. Participants receiving any of the following substances:
1. Systemic immunosuppressive medications or cytotoxic medications within 12 weeks before enrollment \[with the exception of a short course of corticosteroids (≤14 days duration or a single injection) for a self-limited condition at least two (2) weeks before enrollment; inhaled, intranasal or topical steroids are not considered exclusionary\].
2. Receipt of any live-attenuated vaccines within 28 days before or after VLP vaccination.
3. Receipt of medically indicated non-live vaccine, (e.g. influenza, pneumococcal), or allergy treatment with antigen injections, planned for administration seven (7) days before or after study vaccine administration.
14. Participant has a positive urine drug toxicology at screening for drugs of abuse defined as Amphetamines, Barbiturates, Benzodiazepines, Cocaine Metabolite, Opiates, Oxycodone, Phencyclidine without confirmation of medical need (e.g. anxiolytics or pain medications).
15. Women with a positive pregnancy test at screening, vaccination day or challenge day.
16. HIV infection, by screening and confirmatory assays.
17. Participant is seropositive for Hepatitis B surface antigen (HBsAg) or positive for Hepatitis C RNA at screening.
18. Participant has definite plans to travel to a dengue-endemic area during the study.
19. Participant has history or documentation of previous infection with DENV, ZIKV, WNV, JEV, YFV, or St. Louis encephalitis virus (SLEV). Previous infection with DENV, ZIKV, WNV or YFV will be determined by neutralizing antibody assay performed within 60 days of enrollment, medical record, or vaccination record. JEV or SLEV infection will be assessed based on participant history and available medical records. JEV vaccination history will also be reviewed.
20. History of a severe allergic reaction or anaphylaxis.
21. History of allergy to hygromycin.
22. Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination.
23. Anticipated receipt of any investigational agent in the 28 days before or through the duration of the trial.
24. Refusal to allow storage of specimens for future research.
25. Participant is a JHU student currently enrolled in a coursework, an internship, or clinical hours where the supervisor or instructor of record is employed by the Center for Immunization Research.
26. Participant is faculty or staff currently employed by the Center for Immunization Research.
