Safety of an Oral HIV Vaccine in HIV Uninfected Volunteers
| Status: | Not yet recruiting |
|---|---|
| Conditions: | HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - 55 |
| Updated: | 4/2/2016 |
| Contact: | George K. Lewis, PhD |
| Email: | lewisg@umbi.umd.edu |
| Phone: | 410- 706-4688 |
Development of an Oral Prime-Boost AIDS Vaccine to Elicit Broadly Neutralizing Antibodies Against HIV-1
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 vaccine contains
only one of the many substances that HIV needs to make more copies of itself, so the vaccine
itself cannot cause HIV or AIDS.
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 vaccine contains
only one of the many substances that HIV needs to make more copies of itself, so the vaccine
itself cannot cause HIV or AIDS.
The transmission of HIV-1 by both sexual and parenteral 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 (SCBaL/M9) in healthy human volunteers. This will be the first
study in volunteers to use an intracellular 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 conformationally 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 comprised 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 brief medical interview, physical exam, blood and urine tests, and
counseling on avoiding HIV infection and pregnancy. Participants will be tested for HIV
infection 3 times during the study.
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 (SCBaL/M9) in healthy human volunteers. This will be the first
study in volunteers to use an intracellular 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 conformationally 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 comprised 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 brief medical interview, physical exam, blood and urine tests, and
counseling on avoiding HIV infection and pregnancy. Participants will be tested for HIV
infection 3 times during the study.
Inclusion Criteria
- HIV uninfected
- Low risk sexual behavior
- Negative for Hepatitis B surface antigen
- Negative for Hepatitis C viral sequences and antibody
- Availability for follow-up for planned duration of the study (12 months)
- Acceptable methods of contraception
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 surgical excision followed by a sufficient
observation period to give a reasonable assurance of cure
- Medical or psychiatric condition or occupational responsibilities which 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
- Live attenuated vaccines within 60 days of study entry. Medically indicated killed or
subunit vaccines (e.g., influenza, pneumococcal) are not exclusionary, but should be
given at least 2 weeks away from HIV immunizations.
- Use of experimental agents within 30 days of study entry
- Receipt of blood products or immunoglobulin within 6 months of study entry
- Active syphilis
- Active tuberculosis
- History of anaphylaxis or 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)
- Pregnant or breastfeeding
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