Immunogenicity and Safety of Hecolin® in HIV Positive/Negative Adults and in Children

Inclusion Criteria (healthy participants only):

1. Healthy participants 2 to 45 years of age at enrollment,

2. Participants/Parent(s)/LAR who have voluntarily given informed consent/assent,

3. Participants/Parent(s)/LAR willing to follow the study procedures and available forthe entire duration of the study and agrees to the collection of all biospecimens,

4. HIV negative,

5. Not pregnant,

6. Agreement to practice effective contraception for female participants ofchildbearing potential and non-sterile males until at least 8 months after the firstvaccination.

7. Has practiced adequate contraception or has abstained from all activities that couldresult in pregnancy for at least 28 days prior to the first dose of vaccine, and

8. Female participant not currently breastfeeding.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Has received any hepatitis E vaccine in the past,

2. Febrile illness (body temperature ≥ 38°C) or acute illness within 3 days prior tothe study vaccination,

3. Known history or allergy to study vaccine components and/or excipients or othermedications, or any other allergies or medical history deemed by the investigator toincrease the risk of an adverse event if they were to participate in the trial (e.g., Guillain-Barre Syndrome),

4. Major congenital abnormalities which in the opinion of the investigator may affectthe participant's participation in the study,

5. Known history of immune function disorders including immunodeficiency diseases (known HIV infection or other immune function disorders) and lupus,

6. Chronic use of systemic steroids (>2 mg/kg/day or >20 mg/day prednisone equivalentfor periods exceeding 10 days), cytotoxic or other immunosuppressive drugs withinthe past 6 weeks,

7. Any abnormality or chronic disease which in the opinion of the investigator might bedetrimental to the safety of the participant and interfere with the assessment ofthe study objectives,

8. Behavioral or cognitive impairment, chronic substance abuse, or psychiatric diseaseor neural disorders, that, in the opinion of the investigator, could interfere withthe participant's ability to participate in the trial,

9. History of splenectomy,

10. History of thrombocytopenia and/or thrombosis, myocarditis or pericarditis or anyother significant cardiac condition,

11. With a known bleeding diathesis or any condition that may be associated with aprolonged bleeding time resulting in contraindication for IM injections/bloodextractions.,

12. Receipt of blood or blood-derived products in the past 3 months,

13. Receipt of other vaccines from 4 weeks prior to test vaccination or planned toreceive any vaccine within 4 weeks of last dose of study vaccine,

14. Concomitantly enrolled or scheduled to be enrolled in another trial,

15. Research staff involved with the clinical study or family/household members ofresearch staff,

16. Body mass index (BMI) of ≥ 40 in adults and for children a BMI- index-for-age is ≥95th percentile, at the time of the screening visit, or

17. As per the Investigator's medical judgement, an individual could be excluded fromthe study despite meeting all inclusion/exclusion criteria mentioned above.

Inclusion criteria for HIV-positive arm:

1. Adults 18-45 years living with HIV on anti-retroviral (ARV) treatment and willing tohave CD4 and viral load measured as per protocol,

2. Able to provide a voluntary signed informed consent,

3. Participants willing to follow the study procedures of the study and available forthe entire duration of the study and agrees to the collection of all biospecimens,

4. Agreement to practice effective contraception for female participants ofchildbearing potential and non-sterile males until at least 3 months after the lastvaccination.

5. Has practiced adequate contraception or has abstained from all activities that couldresult in pregnancy for at least 28 days prior to the last dose of vaccine, and

6. Female participant is currently not breastfeeding.

Exclusion Criteria for HIV-positive arm:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Has received any hepatitis E vaccine in the past,

2. Newly diagnosed HIV-positive (diagnosed on screening) on ARVs for 0-4 weeks (Note:These participants can be re-screened and enrolled once they have been on ARVs for 4weeks),

3. Febrile illness (body temperature ≥ 38°C) or acute illness within 3 days prior tothe study vaccination,

4. Serious adverse reaction to any vaccine, or any component of the investigationalvaccine, including a history of anaphylaxis and symptoms of a severe allergicreaction and history of allergies in the past,

5. Current hospitalization,

6. History of inherited blood disorders, heparin-induced thrombocytopenia, orthromboembolic disorders,

7. History of any blood product transfusion up to 6 months before enrolment,

8. Receipt of other vaccines from 4 weeks prior to test vaccination or planned toreceive any vaccine within 4 weeks of last dose of study vaccine

9. Currently taking anti-coagulation therapy, or chronic aspirin in the past 3 months,

10. Pregnant or breastfeeding women throughout the study period,

11. Extreme obesity (defined as BMI of 40 kg/m2 or higher),

12. Chronic kidney disease requiring dialysis,

13. Liver disease (Note mild chronic liver disease is not an exclusion criterion),

14. Participants with acquired or hereditary immunodeficiencies other than HIV,

15. History of hereditary, idiopathic, or acquired angioedema,

16. No spleen or functional asplenia,

17. Platelet disorder or other bleeding disorder that may cause injectioncontraindication,

18. Chronic use (more than 14 continuous days) of any medications that may be associatedwith impaired immune responsiveness including, but not limited to, systemiccorticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections,immunoglobulin, interferon, or immunomodulators. The use of low dose topical,ophthalmic, inhaled, and intranasal steroid preparations will be permitted,

19. According to the judgement of the investigator, the participant has any otherfactors that might interfere with the results of the clinical trial or poseadditional risk due to participation in the study,

20. Assessed by the Investigator to be unable or unwilling to comply with therequirements of the protocol