A Phase I Safety and Immunogenicity Trial of HIV-1 gp120 C4-V3 Hybrid Polyvalent Peptide Immunogen Mixed in Mineral Oil Containing Mannose Mono-Oleate (IFA)

A Phase I Safety and Immunogenicity Trial of HIV-1 gp120 C4-V3 Hybrid Polyvalent Peptide Immunogen Mixed in Mineral Oil Containing Mannose Mono-Oleate (IFA)

To evaluate the safety of HIV-1 gp120 C4-V3 hybrid polyvalent peptide immunogen (C4-V3 peptides) formulated in mineral oil containing mannose mono-oleate (IFA) in HIV-1 uninfected volunteers. To evaluate the humoral and cellular immune responses to the C4-V3 peptides as measured by the induction of 1 or more of the following: neutralizing antibodies to HIV-1 MN and RF, cross-neutralizing antibodies to primary isolates of HIV-1, HIV-1 antigen-specific lymphoproliferation, CD8+ and CD4+ cytotoxic T lymphocyte (CTL) activity specific for HIV-1 gp120 or V3 peptides corresponding to the vaccine strains of HIV-1, induction of HLA-B7 and HLA-A2 restricted CD8+CTLs, and induction of HIV-specific DTH responses.

The test immunogen (C4-V3 peptides) is constructed from 4 sequences of the HIV-1 V3 gp120 loop shared by approximately 80% of North American HIV-1 strains. Because of the critical role that this region plays in generating anti-HIV sequences, it is hypothesized that the test immunogen (C4-V3 peptides) will be capable of inducing a broad range of cross-reactive neutralizing antibodies in the majority of recipients.

The test immunogen (C4-V3 peptides) is constructed from 4 sequences of the HIV-1 V3 gp120 loop shared by approximately 80% of North American HIV-1 strains. Because of the critical role that this region plays in generating anti-HIV sequences, it is hypothesized that the test immunogen (C4-V3 peptides) will be capable of inducing a broad range of cross-reactive neutralizing antibodies in the majority of recipients.

Twenty-eight volunteers are randomized to receive two 0.5 ml injections of C4-43 peptides in IFA or placebo (IFA alone) administered intramuscularly at 0, 1, 6, and 12 months. At least 50% of all volunteers (6 per Groups I and II; 2, Group III) must be HLA-B7 phenotype.

Inclusion Criteria

Volunteers must have:

• Negative ELISA for HIV within 8 weeks of immunization.
• Normal history and physical examination.
• Normal chest x-ray within 4 weeks prior to initial immunization.
• Low-risk sexual behavior as defined by AVEG.

Exclusion Criteria

Co-existing Condition:

Volunteers with the following conditions are excluded:

• Medical or psychiatric condition that precludes compliance with the protocol, including recent suicidal ideation or present psychosis.
• Occupational responsibilities which preclude compliance with the protocol.
• Active syphilis (if the serology is documented to be a false positive or due to a remote [more than 6 months] treated infection, the volunteer is eligible).
• Active tuberculosis (volunteers with a positive purified protein derivative and a normal chest x-ray showing no evidence of TB and not requiring isoniazid therapy are eligible).
• Positivity for hepatitis B surface antigen.

Volunteers with the following prior conditions are excluded:

• History of immunodeficiency, chronic illness, malignancy, or autoimmune disease. NOTE: Individuals with a history of cancer are excluded unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure.
• History of suicide attempts or past psychosis.
• History of anaphylaxis or other serious adverse reactions to vaccines.
• History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., Stevens-Johnson syndrome, bronchospasm, or hypotension).
• History of lung disease.

Prior Medication:

Excluded:

• Live attenuated vaccines within 60 days of study. NOTE: Medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) are not exclusionary, but should be given at least 2 weeks away from HIV immunizations.
• Experimental agents within 30 days prior to study.
• HIV-1 vaccines or placebo, received in a previous HIV vaccine trial.
• Immunosuppressive medications.

Prior Treatment:

Excluded:

• Receipt of blood products or immunoglobulin in the past 6 months.

Risk Behavior: Excluded:

• Alcohol intake greater than or equal to the equivalent of 1 oz of 100 proof per day (4 oz. glass of wine or 12 oz. of beer per day).
• Identifiable higher-risk behavior for HIV infection as determined by screening questions designed to identify risk factors for HIV infection; specific exclusions include a history of injection drug use within the last 12 months prior to enrollment and higher- or immediate-risk sexual behavior as defined by the AVEG (i.e., meeting the criteria for AVEG Risk Groups C and D).