Development of a New HIV Vaccine

HIV Infections Clinical Trial

Official title:

Evaluation of the Safety of a Polyvalent Vaccinia Virus HIV-1 Envelope Recombinant Vaccine (PolyEnv1) in Healthy Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00051922
• Other study ID #: P01AI045142
• Secondary ID: P01AI045142
• Status: Completed
• Phase: Phase 1
• First received: January 17, 2003
• Last updated: June 6, 2011
• Start date: October 1997
• Est. completion date: June 2009

Study information

• Verified date: June 2011
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine the safety of a new HIV vaccine and to evaluate the immune response to the vaccine. Only some HIV genes are used to make the vaccine and therefore the vaccine cannot itself cause HIV or AIDS.

Description:

HIV-1 presents several challenges to vaccine design, including: 1) high mutation rates resulting in tremendous diversity of virus envelope, the target of neutralizing antibody, such that antibody elicited to one envelope may not protect from virus with a distinct envelope; 2) envelope from infected persons differs from envelopes obtained from T-cell line cultures, the usual source of envelope for vaccines; and 3) envelope glycoprotein exists as oligomers on the virion surface, not as the monomers used in previous vaccines. This study will test a new vaccine that has been designed to meet these challenges by delivering diverse, patient-derived, oligomeric envelopes to induce multiple type-specific responses capable of recognizing native envelope on natural variants. The vaccine vector used in this vaccine trial is recombinant vaccinia virus based on the NYCDH vaccinia isolate.

Participants in this study will receive the PolyEnv1 HIV vaccine and will be followed for one year. Laboratory tests will be performed at 10 study visits to monitor the participants' immunologic response and assess the safety of the vaccine. Patients will also have numerous HIV tests throughout the study period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2009
• Est. primary completion date: July 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 32 Years

Eligibility

Inclusion Criteria:

• HIV-1 negative

• Availability for one year of follow-up

• No evidence of previous smallpox vaccination

• Acceptable methods of contraception

Exclusion Criteria:

• Immunosuppressive or chronic illness

• Medical or psychological conditions which could affect compliance

• High risk for HIV infection

• Live attenuated vaccines within 60 days

• Experimental agents within 30 days

• Blood products within past 6 months

• Eczema

• Pregnant or lactating women

• Household contact with immunodeficient person, pregnant woman, or child less than 12 months of age

• Allergy to gentamicin

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• PolyEnv1
Recombinant vaccinia virus vaccine

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (11)

Brown SA, Stambas J, Zhan X, Slobod KS, Coleclough C, Zirkel A, Surman S, White SW, Doherty PC, Hurwitz JL. Clustering of Th cell epitopes on exposed regions of HIV envelope despite defects in antibody activity. J Immunol. 2003 Oct 15;171(8):4140-8. — View Citation

Caver TE, Lockey TD, Srinivas RV, Webster RG, Hurwitz JL. A novel vaccine regimen utilizing DNA, vaccinia virus and protein immunizations for HIV-1 envelope presentation. Vaccine. 1999 Mar 17;17(11-12):1567-72. — View Citation

Lockey TD, Slobod KS, Caver TE, D'Costa S, Owens RJ, McClure HM, Compans RW, Hurwitz JL. Multi-envelope HIV vaccine safety and immunogenicity in small animals and chimpanzees. Immunol Res. 2000;21(1):7-21. — View Citation

Rencher SD, Lockey TD, Srinivas RV, Owens RJ, Hurwitz JL. Eliciting HIV-1 envelope-specific antibodies with mixed vaccinia virus recombinants. Vaccine. 1997 Feb;15(3):265-72. Erratum in: Vaccine 2000 Mar 17;18(18):1969. Vaccine. 2010 Apr 26;28(19):3507. — View Citation

Rencher SD, Slobod KS, Dawson DH, Lockey TD, Hurwitz JL. Does the key to a successful HIV type 1 vaccine lie among the envelope sequences of infected individuals? AIDS Res Hum Retroviruses. 1995 Sep;11(9):1131-3. — View Citation

Richmond JF, Mustafa F, Lu S, Santoro JC, Weng J, O'Connell M, Fenyö EM, Hurwitz JL, Montefiori DC, Robinson HL. Screening of HIV-1 Env glycoproteins for the ability to raise neutralizing antibody using DNA immunization and recombinant vaccinia virus boosting. Virology. 1997 Apr 14;230(2):265-74. — View Citation

Slobod KS, Bonsignori M, Brown SA, Zhan X, Stambas J, Hurwitz JL. HIV vaccines: brief review and discussion of future directions. Expert Rev Vaccines. 2005 Jun;4(3):305-13. Review. — View Citation

Slobod KS, Coleclough C, Brown SA, Stambas J, Zhan X, Surman S, Jones BG, Zirkel A, Freiden PJ, Brown B, Sealy R, Bonsignori M, Hurwitz JL. Clade, Country and Region-specific HIV-1 Vaccines: Are they necessary? AIDS Res Ther. 2005 Apr 28;2(1):3. — View Citation

Slobod KS, Lockey TD, Howlett N, Srinivas RV, Rencher SD, Freiden PJ, Doherty PC, Hurwitz JL. Subcutaneous administration of a recombinant vaccinia virus vaccine expressing multiple envelopes of HIV-1. Eur J Clin Microbiol Infect Dis. 2004 Feb;23(2):106-1 — View Citation

Surman S, Lockey TD, Slobod KS, Jones B, Riberdy JM, White SW, Doherty PC, Hurwitz JL. Localization of CD4+ T cell epitope hotspots to exposed strands of HIV envelope glycoprotein suggests structural influences on antigen processing. Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4587-92. Epub 2001 Apr 3. — View Citation

Zhan X, Slobod KS, Surman S, Brown SA, Lockey TD, Coleclough C, Doherty PC, Hurwitz JL. Limited breadth of a T-helper cell response to a human immunodeficiency virus envelope protein. J Virol. 2003 Apr;77(7):4231-6. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tolerability and safety of the PolyEnv1 vaccine		Throughout study	Yes

External Links

•   Click here for more information about St. Jude Children's Research Hospital.
•   Click here for more information on HIV preventive vaccines