A Phase I, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Immunogenicity of HIV-1 MN rsgp120 and Bivalent AIDSVAX B/E (HIV-1 MN rgp120/A244 rgp120) in Combination With QS-21 With or Without Alum in Healthy HIV-1 Uninfected Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 4
研究概览
简要总结
To assess the safety and immune response to two experimental vaccines when formulated with QS-21 or QS-21 plus alum. To determine whether the new preparation of QS-21 in polysorbate 80 is less reactogenic than the QS-21 formulation used in AVEG Protocols 016, 016A, and 016B. To examine whether QS-21 is immunologically equivalent to that used in 16B. To determine if QS-21, when given with low doses of antigen, induces measurable HIV-1-specific CTL activity. To evaluate if the QS-21 dose-sparing effect extends to an antigen dose of 0.5 micrograms. To determine if the bivalent vaccine gives responses equivalent to the monovalent product or if a broadening of the HIV-1-specific binding and neutralizing antibody responses occurs.
An effective vaccine to prevent HIV-1 infection may need to generate diverse and multifaceted immunologic responses. Required parts of the immune response may include: humoral antibodies, which broadly neutralize non-syncytium-inducing strains of HIV-1; T cell help provided by both CD4 and CD8 positive subsets; and a class I-restricted cytotoxic lymphocyte response. Other effector responses, such as the generation of antibody-dependent cellular cytotoxicity, cytokines, chemokines, or other antiviral factors may also be critical in mounting protective immunity. Given the lack of a surrogate immunologic marker, the most practical approach for possible efficacy trials would be to evaluate a candidate vaccine that elicits as many of these responses as possible.
详细描述
An effective vaccine to prevent HIV-1 infection may need to generate diverse and multifaceted immunologic responses. Required parts of the immune response may include: humoral antibodies, which broadly neutralize non-syncytium-inducing strains of HIV-1; T cell help provided by both CD4 and CD8 positive subsets; and a class I-restricted cytotoxic lymphocyte response. Other effector responses, such as the generation of antibody-dependent cellular cytotoxicity, cytokines, chemokines, or other antiviral factors may also be critical in mounting protective immunity. Given the lack of a surrogate immunologic marker, the most practical approach for possible efficacy trials would be to evaluate a candidate vaccine that elicits as many of these responses as possible.
Volunteers in each of 5 groups receive vaccine or placebo by intramuscular injection at Months 0, 1, and 6. All patients receive one of two doses of QS-21 along with vaccine or placebo and some groups receive alum as follows:
Group 1: low-dose MN rsgp120/HIV-1 plus QS-21 (13 volunteers). Group 2: high-dose MN rsgp120/HIV-1 plus QS-21 (13 volunteers). Group 3: AIDSVAX B/E (injection contains each of the two vaccine components, HIV-1 MN rgp120 and A244 rgp120/HIV-1) plus QS-21 plus alum (13 volunteers).
Group 4: high-dose MN rgp120/HIV-1 plus QS-21 plus alum (13 volunteers). Group 5: placebo plus QS-21 (8 volunteers). Volunteers will be closely monitored after each immunization and followed for a minimum of 12 months after the initial immunization.
研究设计
- 研究类型
- Interventional
- 主要目的
- Prevention
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Volunteers must have:
- •Negative ELISA for HIV within 8 weeks prior to immunization.
- •CD4 count greater than or equal to 400 cells/mm
- •Normal history and physical examination. [Refer to Laboratory values for additional requirements.]
排除标准
- •Co-existing Condition:
- •Volunteers with the following conditions or symptoms are excluded:
- •Medical or psychiatric conditions or occupational responsibilities which preclude subject compliance with the protocol.
- •Recent suicidal ideation or psychosis.
- •Active syphilis. NOTE: If the serology is documented to be a false positive or due to a remote (greater than 6 months) treated infection, the volunteer is eligible.
- •Active tuberculosis. NOTE: Volunteers with a positive PPD and a normal chest x-ray showing no evidence of TB and not requiring INH therapy are eligible.
- •Positive for hepatitis B surface antigen.
- •Volunteers with the following prior conditions are excluded:
- •History of immunodeficiency, chronic illness, or autoimmune disease.
- •History of cancer unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure.
- •History of suicide attempts, recent suicidal ideation, or past or present psychosis.
- •History of anaphylaxis or other serious adverse reactions to vaccines.
- •History of serious allergic reaction to any substance requiring hospitalization or emergency medical care (e.g., Stevens-Johnson syndrome, bronchospasm, or hypotension).
- •History of reaction to thimerosal.
- •Prior Medication:
- •Live attenuated vaccine 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 as part of a previous HIV vaccine trial.
- •Prior Treatment:
- •Blood products or immunoglobulin in the past 6 months.
- •Experimental agents within 30 days prior to study.
- •Risk Behavior:
- •Volunteers with an identifiable higher- or intermediate-risk sexual behavior for HIV infection (i.e., AVEG Risk Groups C or D ).
- •History of intravenous drug use within 12 months prior to enrollment.