This is a randomized, double-blind, placebo-controlled study. Eligible subjects will be randomized in a 1:1 ratio to receive GEN-004 with adjuvant or placebo. Each subject will receive up to 3 doses at 4 week intervals.

Following the third dose, subjects will be inoculated intranasally with S. pneumoniae serotype 6B. Nasal washes to identify S. pneumoniae colonization will be obtained pre-inoculation, and then 2, 7 and 14 days after inoculation.

Subjects will also be monitored for safety and tolerability throughout the dosing period, and then for 12 months after their last dose.

The purpose of this study is to evaluate the effectiveness of GEN-004 in reducing colonization rates and magnitude of colonization following the S. pneumoniae challenge.

Inclusion Criteria:

• Males and non-pregnant females, ages 18 to 55 years inclusive.
• Willing and able to provide written informed consent.
• Fluent English speakers only (for safety reasons)
• Willing to perform and comply with all study procedures including attending clinic visits as scheduled.

Exclusion Criteria:

• Prior vaccination with pneumococcal vaccine.
• History of invasive pneumococcal disease (i.e., sepsis, meningitis or pneumonia with bacteremia).
• Close contact with at risk individuals (young children [under 5years], immunosuppressed adults, elderly, chronic ill health).
• Current smoker or significant smoking history (>10 pack years).
• Pregnant or breast-feeding woman.
• Women of child-bearing potential (WOCBP) who are deemed not to have sufficient, effective birth control in place for 1 month prior to vaccination and 1 month after the final vaccination.
• Allergy to penicillin or amoxicillin.
• Any screening laboratory value > Grade 1
• Positive serologic test for HIV-1 or hepatitis C infection; positive hepatitis B surface antigen (HBsAg).
• Asthma (on regular medication) or other respiratory disease.
• Immunocompromised individuals, including those receiving corticosteroids or other immunosuppressive agents.
• Presence or history of auto-immune disease (refer to Appendix 4) regardless of current treatment.
• No antibiotic treatment within 1 week of inoculation
• Previous involvement in EHPC study inoculated with pneumococcal bacteria
• In any other clinical trial unless in observational stage or follow-up
• Diabetes, type 1 or type 2.
• Other active, uncontrolled co-morbidities that, in the opinion of the Investigator would make the subject unsuitable for the study or unable to comply with the study requirements.

NOTE: Subjects who are taking a medication to control an underlying co-morbidity may be enrolled if there have been no changes to their medication within 60 days prior to first dose of Study Drug.