Consider this summary of a proposed research project:
This study will test the safety of and immune response to an oral HIV vaccine in healthy volunteers. The vaccine in this study uses a weakened bacterium called Salmonella typhi to deliver an HIV gene into the body through the mouth. The body then produces an HIV protein from the gene; this protein stimulates an anti-HIV immune response.
The transmission of HIV-1 by both sexual and parenteral (directly through the blood via IV needle) routes makes it likely that a successful preventive vaccine against this virus will need to induce protective immunity in both mucosal and systemic compartments. The long-term objective of this program is to develop an HIV-1 vaccine that elicits protective immunity in both the mucosal and systemic compartments.
The study will evaluate the safety and immunogenicity of an oral recombinant Salmonella typhi HIV-1 gp120 vaccine in healthy human volunteers. This will be the first study in volunteers to use a bacterium to deliver a recombinant vector vaccine mucosally.
The study will also develop an Env immunogen that elicits a broader spectrum of neutralizing antibodies than gp120 and that can be delivered by Salmonella typhi or as a soluble protein immunogen.
This is a Phase I dose-escalation study of two vaccine components that will be combined in a larger prime-boost protocol should the desired safety endpoints be obtained. Both components use a constrained gp120 that expresses epitopes recognized by broadly neutralizing antibodies. The priming immunogen will be the conformationally constrained gp120 gene delivered orally by live attenuated Salmonella typhi. The boosting immunogen will be a soluble subunit protein made up solely of the conformationally constrained gp120.
All participants in this study will receive the vaccine. Participants will be randomized to different vaccine doses. Participants will have eight study visits over 20 weeks. Study visits will include a brief medical interview, physical exam, blood and urine tests, and counseling on avoiding HIV infection and pregnancy. Participants will be tested for HIV infection three times during the study.
Inclusion Criteria:
HIV uninfected.Sexual behavior that is indicative of low risk for HIV infection.Negative for Hepatitis B surface antigen.Negative for Hepatitis C viral sequences and antibody.Availability for follow-up during the study (five months).Willingness to use acceptable methods of contraception during study period.
Exclusion Criteria:
Receipt of HIV vaccines or placebo in a previous HIV vaccine trial.History of immunodeficiency, chronic illness, autoimmune disease, or use of immunosuppressive medications.History of cancer unless there has been a surgical excision followed by a sufficient observation period to give a reasonable assurance of cure.Medical or psychiatric condition or occupational responsibilities that preclude compliance with the protocol.History of suicide attempts, recent suicidal ideation, or psychosis.High-risk behavior for HIV infection as determined by screening questionnaire.History of injection drug use within 12 months of study entry.Use of experimental agents within 30 days of study entry.Receipt of blood products or immunoglobulin within six months of study entry.Active syphilis.Active tuberculosis.History of anaphylaxis or serious adverse reactions to vaccines.Pregnant or breastfeeding.
If you are on the IRB reviewing this proposal, what matters might you consider following the principles in the Belmont Report? Cite at least one principle. How might the composition of your IRB effect the outcome? Which form of consent would you recommend (see list of consent types in reading)? Explain
