A Study to Determine the Safety and Immunogenicity of Bivalent GI.1 and GII.4 Vaccines in Healthy Volunteers

Key Inclusion Criteria

To be eligible for this study, subjects must meet all the following:

• In stable and good general health, without significant medical illness, based on medical history, physical examination, and vital signs at screening based on investigator judgement.
• Body mass index (BMI) between >/= 17.0 and </= 35.0 kg/m2 at screening SNG.
• Available for all planned visits and tele-health appointment, and willing to complete all protocol-defined procedures and assessments (including ability and willingness to swallow multiple small enteric-coated tablets per study dose).
• Female subjects must not be breastfeeding and must provide a negative pregnancy test at screening and pre-dose.
• Female subjects must fulfill one of the following criteria:

i. At least 1 year post-menopausal (defined as amenorrhea for greater than or equal to 12 consecutive months prior to screening without alternative medical cause) or surgically sterile.

ii. Female subjects of childbearing potential must be willing to use a highly effective form of contraception for 30 days prior to initial vaccination and until 60 days after last vaccination. Acceptable forms are oral, implantable, intrauterine, transdermal, intravaginal, injectable, double barrier or abstinence (subjects using diaphragms must also use condom). The form of contraception must be approved by the investigator.

iii. Male subjects must agree to practice abstinence from heterosexual intercourse or to use an effective method of birth control as noted above from first vaccination to 60 days after last vaccination. Male subjects must agree to refrain from donating sperm and practice abstinence from all intercourse or to use an effective method of double barrier birth control or condom as noted above from first vaccination to 60 days after last vaccination.

• Capable of understanding and giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.

Key Exclusion Criteria

The subjects must be excluded from participating in the study if they meet any of the following:

• Known clotting/bleeding issues and/or personal and family history with increased risk of bleeding or clotting.
• Presence of significant uncontrolled medical or psychiatric illness (acute or chronic) including institution of new medical/surgical treatment or significant dose alteration for uncontrolled symptoms or drug toxicity within 3 months prior to screening and reconfirmed at baseline.
• Cancer, or treatment for cancer or any procedure or preventive medication for cancer or to prevent recurrence, within past 3 years (excluding fully treated and resolved basal cell carcinoma or squamous cell carcinoma)
• Presence of immunosuppression or medical condition possibly associated with impaired immune responsiveness, including diabetes mellitus- type 1 and 2
• History of irritable bowel disease or other inflammatory digestive or gastrointestinal condition that could affect the distribution/safety evaluation of an orally administered vaccine targeting the mucosa of the small intestine. Such conditions may include but are not limited to:

a. Any history of: i. GI malignancy ii. malabsorption iii. pancreatobiliary disorders iv. inflammatory bowel disease v. irritable bowel disease vi. hiatal hernia vii. surgical resection b. History of diagnosis or treatment in past 5 years of: i. esophageal or gastric motility disorder ii. gastro esophageal reflux disorder iii. peptic ulcer iv. cholecystectomy

• History of any form of angioedema
• History of serious reactions to vaccination such as anaphylaxis, respiratory problems, hives or abdominal pain
• Diagnosed bleeding disorder or significant bruising or bleeding difficulties that could make blood draws problematic.
• Any condition that resulted in the absence or removal of the spleen
• Acute disease within 72 hours prior to vaccination defined as the presence of a moderate or severe il