Safety and immunogenicity of a V3 loop synthetic peptide conjugated to purified protein derivative in HIV-seronegative volunteers

Arye Rubinstein, Harris Goldstein, M. Pettoello-Mantovani, Y. Mizrachi, B. R. Bloom, E. Furer, B. Althaus, J. U. Que, T. Hasler, S. J. Cryz

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objectives: To develop a peptide-based model for a preventive vaccine for HIV-1 infection. Design: Phase I trial in HIV-1-seronegative volunteers. Participants: Adult healthy subjects HIV-1-antibody-seronegative in an enzyme-linked immunosorbent assay, screened for tuberculin [purified protein derivative (PPD)] reactivity with 2 tuberculin units PPD-administered intradermally. Interventions: Submicrogram doses of a PPD conjugate with a peptide of the primary neutralizing domain (PND) of HIV-1(MN) (PPD-MN-PND) were administered intradermally to tuberculin skin-test-positive and -negative volunteers. Results: Antibodies to the MN-PND were measured after two immunizations in 10 out of 11 PPD skin-test-positive volunteers. After the fourth immunization high-affinity antibodies were detected, which persisted for over 1 year. High titers of MN-PND-specific immunoglobulin (Ig) G and IgA were detected in the serum and saliva of all volunteers tested. Serum antibodies were cross-reactive with PND peptide from some other HIV-1 strains but neutralized only the HIV-1(MN) prototype. Human leukocyte antigen (HLA)-B7-restricted MN-PND-specific cytotoxic T lymphocytes (CTL) were also detected. Conclusions: The PPD-MN-PND vaccine at submicrogram doses is safe and immunogenic in PPD skin-test-positive healthy adult volunteers. Long lasting humoral immune responses in the serum and saliva were possibly accompanied by HLA-B7-restricted CTL responses. This is a vaccine prototype that can be rapidly and inexpensively modified to include other peptide epitopes. It is especially suitable for use in a worldwide multibillion Bacillus Calmette-Guerin (BCG)-primed or tuberculosis-exposed population at risk for HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)243-251
Number of pages9
JournalAIDS
Volume9
Issue number3
StatePublished - 1995

Fingerprint

HIV-1
Volunteers
HIV
Safety
Peptides
Skin Tests
Proteins
Vaccines
Tuberculin
Cytotoxic T-Lymphocytes
HLA Antigens
Saliva
HIV Infections
Immunization
Healthy Volunteers
Serum
HIV Antibodies
Tuberculin Test
Antibody Affinity
Antibodies

Keywords

  • Peptide AIDS vaccine
  • Phase I trial
  • Primary neutralizing domain
  • Purified protein derivative-conjugated peptide
  • V3 loop

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Rubinstein, A., Goldstein, H., Pettoello-Mantovani, M., Mizrachi, Y., Bloom, B. R., Furer, E., ... Cryz, S. J. (1995). Safety and immunogenicity of a V3 loop synthetic peptide conjugated to purified protein derivative in HIV-seronegative volunteers. AIDS, 9(3), 243-251.

Safety and immunogenicity of a V3 loop synthetic peptide conjugated to purified protein derivative in HIV-seronegative volunteers. / Rubinstein, Arye; Goldstein, Harris; Pettoello-Mantovani, M.; Mizrachi, Y.; Bloom, B. R.; Furer, E.; Althaus, B.; Que, J. U.; Hasler, T.; Cryz, S. J.

In: AIDS, Vol. 9, No. 3, 1995, p. 243-251.

Research output: Contribution to journalArticle

Rubinstein, A, Goldstein, H, Pettoello-Mantovani, M, Mizrachi, Y, Bloom, BR, Furer, E, Althaus, B, Que, JU, Hasler, T & Cryz, SJ 1995, 'Safety and immunogenicity of a V3 loop synthetic peptide conjugated to purified protein derivative in HIV-seronegative volunteers', AIDS, vol. 9, no. 3, pp. 243-251.
Rubinstein, Arye ; Goldstein, Harris ; Pettoello-Mantovani, M. ; Mizrachi, Y. ; Bloom, B. R. ; Furer, E. ; Althaus, B. ; Que, J. U. ; Hasler, T. ; Cryz, S. J. / Safety and immunogenicity of a V3 loop synthetic peptide conjugated to purified protein derivative in HIV-seronegative volunteers. In: AIDS. 1995 ; Vol. 9, No. 3. pp. 243-251.
@article{0a4b3529248849fca75d861be993c886,
title = "Safety and immunogenicity of a V3 loop synthetic peptide conjugated to purified protein derivative in HIV-seronegative volunteers",
abstract = "Objectives: To develop a peptide-based model for a preventive vaccine for HIV-1 infection. Design: Phase I trial in HIV-1-seronegative volunteers. Participants: Adult healthy subjects HIV-1-antibody-seronegative in an enzyme-linked immunosorbent assay, screened for tuberculin [purified protein derivative (PPD)] reactivity with 2 tuberculin units PPD-administered intradermally. Interventions: Submicrogram doses of a PPD conjugate with a peptide of the primary neutralizing domain (PND) of HIV-1(MN) (PPD-MN-PND) were administered intradermally to tuberculin skin-test-positive and -negative volunteers. Results: Antibodies to the MN-PND were measured after two immunizations in 10 out of 11 PPD skin-test-positive volunteers. After the fourth immunization high-affinity antibodies were detected, which persisted for over 1 year. High titers of MN-PND-specific immunoglobulin (Ig) G and IgA were detected in the serum and saliva of all volunteers tested. Serum antibodies were cross-reactive with PND peptide from some other HIV-1 strains but neutralized only the HIV-1(MN) prototype. Human leukocyte antigen (HLA)-B7-restricted MN-PND-specific cytotoxic T lymphocytes (CTL) were also detected. Conclusions: The PPD-MN-PND vaccine at submicrogram doses is safe and immunogenic in PPD skin-test-positive healthy adult volunteers. Long lasting humoral immune responses in the serum and saliva were possibly accompanied by HLA-B7-restricted CTL responses. This is a vaccine prototype that can be rapidly and inexpensively modified to include other peptide epitopes. It is especially suitable for use in a worldwide multibillion Bacillus Calmette-Guerin (BCG)-primed or tuberculosis-exposed population at risk for HIV-1 infection.",
keywords = "Peptide AIDS vaccine, Phase I trial, Primary neutralizing domain, Purified protein derivative-conjugated peptide, V3 loop",
author = "Arye Rubinstein and Harris Goldstein and M. Pettoello-Mantovani and Y. Mizrachi and Bloom, {B. R.} and E. Furer and B. Althaus and Que, {J. U.} and T. Hasler and Cryz, {S. J.}",
year = "1995",
language = "English (US)",
volume = "9",
pages = "243--251",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Safety and immunogenicity of a V3 loop synthetic peptide conjugated to purified protein derivative in HIV-seronegative volunteers

AU - Rubinstein, Arye

AU - Goldstein, Harris

AU - Pettoello-Mantovani, M.

AU - Mizrachi, Y.

AU - Bloom, B. R.

AU - Furer, E.

AU - Althaus, B.

AU - Que, J. U.

AU - Hasler, T.

AU - Cryz, S. J.

PY - 1995

Y1 - 1995

N2 - Objectives: To develop a peptide-based model for a preventive vaccine for HIV-1 infection. Design: Phase I trial in HIV-1-seronegative volunteers. Participants: Adult healthy subjects HIV-1-antibody-seronegative in an enzyme-linked immunosorbent assay, screened for tuberculin [purified protein derivative (PPD)] reactivity with 2 tuberculin units PPD-administered intradermally. Interventions: Submicrogram doses of a PPD conjugate with a peptide of the primary neutralizing domain (PND) of HIV-1(MN) (PPD-MN-PND) were administered intradermally to tuberculin skin-test-positive and -negative volunteers. Results: Antibodies to the MN-PND were measured after two immunizations in 10 out of 11 PPD skin-test-positive volunteers. After the fourth immunization high-affinity antibodies were detected, which persisted for over 1 year. High titers of MN-PND-specific immunoglobulin (Ig) G and IgA were detected in the serum and saliva of all volunteers tested. Serum antibodies were cross-reactive with PND peptide from some other HIV-1 strains but neutralized only the HIV-1(MN) prototype. Human leukocyte antigen (HLA)-B7-restricted MN-PND-specific cytotoxic T lymphocytes (CTL) were also detected. Conclusions: The PPD-MN-PND vaccine at submicrogram doses is safe and immunogenic in PPD skin-test-positive healthy adult volunteers. Long lasting humoral immune responses in the serum and saliva were possibly accompanied by HLA-B7-restricted CTL responses. This is a vaccine prototype that can be rapidly and inexpensively modified to include other peptide epitopes. It is especially suitable for use in a worldwide multibillion Bacillus Calmette-Guerin (BCG)-primed or tuberculosis-exposed population at risk for HIV-1 infection.

AB - Objectives: To develop a peptide-based model for a preventive vaccine for HIV-1 infection. Design: Phase I trial in HIV-1-seronegative volunteers. Participants: Adult healthy subjects HIV-1-antibody-seronegative in an enzyme-linked immunosorbent assay, screened for tuberculin [purified protein derivative (PPD)] reactivity with 2 tuberculin units PPD-administered intradermally. Interventions: Submicrogram doses of a PPD conjugate with a peptide of the primary neutralizing domain (PND) of HIV-1(MN) (PPD-MN-PND) were administered intradermally to tuberculin skin-test-positive and -negative volunteers. Results: Antibodies to the MN-PND were measured after two immunizations in 10 out of 11 PPD skin-test-positive volunteers. After the fourth immunization high-affinity antibodies were detected, which persisted for over 1 year. High titers of MN-PND-specific immunoglobulin (Ig) G and IgA were detected in the serum and saliva of all volunteers tested. Serum antibodies were cross-reactive with PND peptide from some other HIV-1 strains but neutralized only the HIV-1(MN) prototype. Human leukocyte antigen (HLA)-B7-restricted MN-PND-specific cytotoxic T lymphocytes (CTL) were also detected. Conclusions: The PPD-MN-PND vaccine at submicrogram doses is safe and immunogenic in PPD skin-test-positive healthy adult volunteers. Long lasting humoral immune responses in the serum and saliva were possibly accompanied by HLA-B7-restricted CTL responses. This is a vaccine prototype that can be rapidly and inexpensively modified to include other peptide epitopes. It is especially suitable for use in a worldwide multibillion Bacillus Calmette-Guerin (BCG)-primed or tuberculosis-exposed population at risk for HIV-1 infection.

KW - Peptide AIDS vaccine

KW - Phase I trial

KW - Primary neutralizing domain

KW - Purified protein derivative-conjugated peptide

KW - V3 loop

UR - http://www.scopus.com/inward/record.url?scp=0028956543&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028956543&partnerID=8YFLogxK

M3 - Article

C2 - 7755912

AN - SCOPUS:0028956543

VL - 9

SP - 243

EP - 251

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 3

ER -