This is a Phase 1, open-label, dose-escalation clinical trial to evaluate the safety, reactogenicity, and immunogenicity of the Sm-p80+GLA-SE vaccine candidate in healthy adults between 18 and 55 years of age. Forty-five subjects will receive a series of three intramuscular injections 28 days apart with dose based on group. Five treatment groups, each including nine subjects, will receive three intramuscular (IM) injections of 0.5 mL of the designated study product on either Days 1, 29, and 57 or on Days 1, 29, and 180 (Table 1). Group A (unadjuvanted comparator) will receive 100 micrograms Sm-p80 alone on Days 1, 29, and 57, Group B (low dose standard schedule) will receive 10 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29 and 57, Group C (mid dose delayed booster) will receive 30 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29 and 180, Group D (mid dose standard schedule) will receive 30 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29, and 57, and Group E (high dose standard schedule) will receive 100 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29 and 57. Study duration is approximately 20 months and will be conducted at one site in the US. Participant duration for subjects is 15 months. The primary objective is to assess the safety and reactogenicity following receipt of three doses of 1) 100 micrograms Sm- p80 (unadjuvanted), 2) 10 micrograms Sm-p80 + 5 micrograms GLA-SE, 3) 30 micrograms Sm-p80 + 5 micrograms GLA- SE, and 4) 100 micrograms Sm-p80 + 5 micrograms GLA-SE administered intramuscularly on Days 1, 29, and 57 and 5) 30 micrograms Sm-p80 + 5 micrograms GLA- SE administered on Days 1, 29, and 180.

This is a Phase 1, open-label, dose-escalation clinical trial to evaluate the safety, reactogenicity, and immunogenicity of the Sm-p80+GLA-SE vaccine candidate in healthy adults between 18 and 55 years of age. Forty-five subjects will receive a series of three intramuscular injections 28 days apart with dose based on group. Five treatment groups, each including nine subjects, will receive three intramuscular (IM) injections of 0.5 mL of the designated study product on either Days 1, 29, and 57 or on Days 1, 29, and 180 (Table 1). Group A (unadjuvanted comparator) will receive 100 micrograms Sm-p80 alone on Days 1, 29, and 57, Group B (low dose standard schedule) will receive 10 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29 and 57, Group C (mid dose delayed booster) will receive 30 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29 and 180, Group D (mid dose standard schedule) will receive 30 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29, and 57, and Group E (high dose standard schedule) will receive 100 micrograms Sm-p80 + 5 micrograms GLA-SE on Days 1, 29 and 57. Study duration is approximately 20 months and will be conducted at one site in the US. Participant duration for subjects is 15 months. The primary objective is to assess the safety and reactogenicity following receipt of three doses of 1) 100 micrograms Sm- p80 (unadjuvanted), 2) 10 micrograms Sm-p80 + 5 micrograms GLA-SE, 3) 30 micrograms Sm-p80 + 5 micrograms GLA- SE, and 4) 100 micrograms Sm-p80 + 5 micrograms GLA-SE administered intramuscularly on Days 1, 29, and 57 and 5) 30 micrograms Sm-p80 + 5 micrograms GLA- SE administered on Days 1, 29, and 180. The secondary objectives are to assess anti- Sm-p80 Immunoglobulin G (IgG) antibody responses for all subjects from samples collected at specified time points.

Inclusion Criteria:

1. Male or non-pregnant female 18 through 55 years of age, inclusive, at the time of consent.

2. Able and willing to participate for the duration of the study and able to understand and comply with planned study procedures.

3. Able and willing to provide written (not proxy) informed consent.

4. Is in good health, as judged by the investigator, and determined by medical history and physical examination*.

   *Existing medical diagnoses or conditions (except those in the Subject Exclusion Criteria) must be deemed as stable. A stable medical condition is defined as no change in prescription medication, dose, or frequency of medication in the last three months (90 days) and health outcomes of the specific disease are considered to be within acceptable limits in the last six months (180 days). Any change due to change of health care provider, insurance company, or that is done for financial reasons, as long as in the same class of medication, will not be considered a violation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site PI or appropriate sub-investigator, will not be considered a violation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site PI or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of solicited events and immunogenicity. Topical, nasal, and inhaled medications (with the exception of some uses of corticosteroids as outlined in the Subject Exclusion Criteria), vitamins, and contraceptives are permitted.

5. Women of childbearing potential* must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to each study product injection.

   *Not sterilized via bilateral tubal ligation, bilateral oophorectomy, or hysterectomy, or, if menopausal, still menstruating or < 1 year of the last menses

6. Women of childbearing potential must have used an acceptable form of contraception* in the 30 days prior to their first study product injection.

   *Acceptable single forms of contraception include abstinence from sexual activity that could lead to pregnancy, monogamous relationship with vasectomized partner who has been vasectomized for six months or more prior to enrollment, successful Essure placement (permanent, non-surgical, non-hormonal sterilization), intrauterine devices, and hormonal methods, including the birth control patch, shot (Depo-Provera), pills, the vaginal ring (NuvaRing), and the contraceptive implant (Nexplanon). Acceptable barrier methods include diaphragm or cervical cap with spermicide and the contraceptive sponge.

7. Women of childbearing potential must agree to continue use of an acceptable form of contraception through 30 days after their last study product injection.

8. Weight >/= 50 kg and body mass index (BMI) < 35.0 kg/m2

9. Vital signs (oral temperature, pulse, and blood pressure) are all within normal protocol-defined ranges.*

   *The normal protocol-defined ranges for vital signs include (a) oral temperature less than 38 degrees C (100.4 degrees F), (b) pulse no greater than 100 bpm, (c) systolic blood pressure 85 to 150 mmHg, inclusive, and (d) diastolic BP </= 100 mmHg.

10. Screening clinical lab values are all within normal protocol-defined reference ranges.

    • The normal protocol-defined ranges for laboratory tests include (a) ALT of < 47 IU/L, (b) creatinine less than or equal to the laboratory upper limit of normal, (c) WBC >/=3.80 x10^3/UL and \

Serious adverse events (SAEs), MAAEs, NOCMCs, and PIMMCs were collected from the time of first study product injection through approximately 12 months after the last study product injection. Solicited AEs were collected from the time of each study product injection through 7 days after each study product injection. Unsolicited AEs were collected from the time of each study product injection through 28 days after the study product injection.