The Safety and Immunogenicity of a Potential HIV Vaccine
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: CN54gp140 mixed with GLA-AF
Intervention description: Each vaccination an intramuscular injection of 100 micrograms CN54gp140 mixed with 5 micrograms GLA-AF
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Human immunodeficiency disease; HIV; Vaccine; CN54gp140; Glucopyranosyl lipid adjuvant; GLA; GLA-AF

Summary:

      The potential HIV vaccine has two components: a protein immunogen based on the coat protein
      of HIV; and an adjuvant which enhances the vaccinee's response to the immunogen. The
      immunogen is CN54gp140, and the adjuvant is glucopyranosyl lipid adjuvant - aqueous
      formulation (GLA-AF).

      We wish to assess the vaccine's safety and immunogenicity (the nature of the immune response
      stimulated by the vaccine) when it is given in two different dose regimens:

      Group A: vaccinations at Months 0, 1, 2 and 6; and Group B: vaccinations at Months 0, 1, 2
      and 12.

      Each dose will be an intramuscular injection of 100 micrograms of CN54gp140 mixed with 5
      micrograms of GLA-AF.

      We will recruit only healthy, HIV-uninfected men and women. We will assess the safety of the
      vaccine by monitoring the occurrence of adverse events in the participants. We will assess
      the immunogenicity of the vaccine by monitoring the immune response to the vaccine in blood
      and in genital mucosal secretion samples.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy male or female, as assessed by medical history, physical exam, and laboratory
             tests;

          -  At least 18 years of age on the day of screening and has not reached his/her 46th
             birthday on the day of first vaccination;

          -  Willing to comply with the requirements of the protocol and available for follow-up
             for the planned duration of the study;

          -  Willing and able to give written informed consent;

          -  Willing to undergo HIV testing, receive HIV test results and be committed to
             maintaining low risk behaviour for the trial duration;

          -  If a female who is sexually active with male partner(s), willing to use an effective
             method of contraception from screening until at least 4 months after the last study
             vaccination [e.g., hormonal contraceptives, consistent record with condoms,
             physiological or anatomical sterility in self or partner, but excluding intrauterine
             device (IUD) which would preclude the collection of cervico-vaginal secretions with
             Softcup];

          -  All female volunteers must be willing to undergo urine pregnancy tests at time points
             indicated in the Schedule of Procedures (Appendices A-B) and must test negative prior
             to each study vaccination;

          -  All sexually active males (unless anatomically sterile or in a monogamous relationship
             with a female partner who uses a documented non-barrier method of birth control) must
             be willing to use an effective method of contraception (e.g., consistent condom use)
             from the day of first vaccination until at least 4 months after the last vaccination;

          -  Willing to forgo donations of blood or any other tissues during the study and, for
             those who test HIV-positive due to trial vaccination (vaccine-induced HIV
             seropositivity), until the anti-HIV antibody titres become undetectable.

          -  Registered with a general practitioner for at least the past three months

        Exclusion Criteria:

          -  Confirmed HIV-1 or HIV-2 infection;

          -  Any clinically relevant abnormality on history or examination including history of
             immunodeficiency or autoimmune disease; use of systemic corticosteroids (the use of
             topical or inhaled steroids is permitted); immunosuppressive, anti-cancer,
             anti-tuberculosis or other medications considered significant by the investigator
             within the previous 6 months;

          -  Any clinically significant acute or chronic medical condition that is considered
             progressive, or in the opinion of the investigator, makes the volunteer unsuitable for
             participation in the study;

          -  Reported risky behaviour for HIV infection within the 6 months prior to vaccination as
             defined by: history of injecting drug use in the previous ten years; gonorrhoea or
             syphilis in the last six months; high risk partner (e.g. injecting drug use, HIV
             positive partner) either currently or within the past six months; unprotected anal
             intercourse in the last six months, outside a relationship with a regular partner
             known to be HIV negative; or unprotected vaginal intercourse in the last six months
             outside a relationship with a regular known/presumed HIV negative partner.

          -  Reported abnormal cervical cytology or previous or ongoing treatment for Cervical
             Intraepithelial Neoplasia;

          -  If female, pregnant or planning a pregnancy within 4 months after last study
             vaccination; or lactating;

          -  Bleeding disorder that was diagnosed by a physician (e.g., factor deficiency,
             coagulopathy or platelet disorder that requires special precautions) (Note: A
             volunteer who states that he or she has easy bruising or bleeding, but does not have a
             formal diagnosis and has intramuscular injections and blood draws without any adverse
             experience, is eligible);

          -  History of splenectomy;

          -  Any of the following abnormal laboratory parameters listed below: haemoglobin <11.0
             g/dL; absolute neutrophil count (ANC) ≤ 1.3 x 109/L; absolute lymphocyte count (ALC) ≤
             0.9 x 109/L; platelets ≤ 125 x 109/L; creatinine >1.1 x upper limit of normal (ULN);
             aspartate aminotransferase >1.25 x ULN; alanine aminotransferase >1.25 x ULN;
             clinically significant abnormal urinalysis dipstick confirmed by microscopy (protein
             2+ or more, blood 2+ or more not due to menses); positive for hepatitis B surface
             antigen (HbsAg), hepatitis C (HCV antibodies) or active syphilis;

          -  Receipt of live-attenuated vaccine within the previous 60 days or planned receipt
             within 60 days after vaccination with Investigational Product; or receipt of other
             vaccine, allergy treatment with antigen injections or tuberculin skin test within the
             previous 14 days or planned receipt within 14 days after vaccination with
             Investigational Product;

          -  Receipt of blood transfusion or blood-derived products within the previous 3 months;

          -  Participation in another clinical trial of an Investigational Product currently,
             within the previous 3 months or expected participation during this study;

          -  Prior receipt of another investigational HIV vaccine candidate (Note: receipt of
             placebo in a previous HIV vaccine trial will not exclude a volunteer from
             participation if documentation is available);

          -  History of severe local or systemic reactogenicity to vaccines (e.g., anaphylaxis,
             respiratory difficulty, angioedema);

          -  Psychiatric condition that compromises safety of the volunteer and precludes
             compliance with the protocol. Specifically excluded are persons with psychoses within
             the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture
             within the past 3 years;

          -  Seizure disorder: a participant who has had a seizure in the last 3 years is excluded.
             (Not excluded: a participant with a history of seizures who has neither required
             medications nor had a seizure for 3 years.);

          -  If female, history of toxic shock syndrome (TSS), which would preclude the use of
             Softcup;

          -  If female, current use of intrauterine device (IUD), which would preclude the use of
             Softcup;

          -  If, in the opinion of the Principal Investigator, it is not in the best interest of
             the volunteer to participate in the trial.