Protection of chimpanzees from high-dose heterologous hiv-1 challenge by dna vaccination

Protection of chimpanzees from high-dose heterologous hiv-1 challenge by dna vaccination

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ABSTRACT Novel approaches for the generation of more effective vaccines for HIV-1 are of significant importance. In this report we analyze the immunogenicity and efficacy of an HIV-1 DNA vaccine encoding _env, rev_ and _gag/pol_ in a chimpanzee model system. The immunized animals developed specific cellular and humoral immune responses. Animals were challenged with a heterologous chimpanzee titered stock of HIV-1 SF2 virus and followed for 48 weeks after challenge. Polymerase chain reaction coupled with reverse transcription (RT-PCR) results indicated infection in the control animal, whereas those animals vaccinated with the DNA constructs were protected from the establishment of infection. These studies serve as an important benchmark for the use of DNA vaccine technology for the production of protective immune responses. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS BOTH CHIMPANZEE ADENOVIRUS-VECTORED AND DNA VACCINES INDUCED LONG-TERM IMMUNITY AGAINST NIPAH VIRUS INFECTION Article Open access 04 November 2023 HETEROLOGOUS VACCINATION REGIMENS WITH SELF-AMPLIFYING RNA AND ADENOVIRAL COVID VACCINES INDUCE ROBUST IMMUNE RESPONSES IN MICE Article Open access 17 May 2021 INFECTIOUS RNA VACCINE PROTECTS MICE AGAINST CHIKUNGUNYA VIRUS INFECTION Article Open access 03 December 2020 REFERENCES * Haynes, B.F., Pantaleo, C.,& Fauci, A.S. Toward an understanding of the correlates of protective immunity to HIV infection. _Science_ 271, 324–328 (1996). Article  CAS  PubMed  Google Scholar  * Pantaleo, G. _et al_. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. _N. Engl. J. Med._ 332, 209–216 (1995). Article  CAS  PubMed  Google Scholar  * Rinaldo, C. _et al_. High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1 infected long-term nonprogressors. _J. Virol._ 69, 5838–5842 (1995). CAS  PubMed  PubMed Central  Google Scholar  * Rowland-Jones, S. _et al_. HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women. _Nature Med._ 1, 59–64 (1995). Article  PubMed  Google Scholar  * Rowland-Jones, S., Nixon, D. & Aldhous, M. HIV-specific cytotoxic T-cell activity in an HIV-exposed but uninfected infant. _Lancet_ 341, 860–861 (1993). Article  CAS  PubMed  Google Scholar  * Ugen, K.E. _et al_. Verticaltransmissionofimmunodeficiency virus type 1: Seroreactivity by maternal antibodies to the carboxy region of the gp41 envelope. _J. Infect. Dis._ 175, 63–69 (1997). Article  CAS  PubMed  Google Scholar  * Ugen, K.E. _et al_. Vertical transmission of human immunodeficiency virus (HIV) infection: Reactivity of maternal sera with glycoprotein 120 and 41 peptides from HIV type 1. _J. Clin. Invest._ 89, 1923–1930 (1992). Article  CAS  PubMed  PubMed Central  Google Scholar  * Rossi, P. _et al_. Presence of maternal antibodies to human immunodeficiency virus 1 envelope glycoprotein gpl 20 epitopes correlates with the uninfected status of children born to seropositive mothers. _Proc. Not. Acad. Sci. USA_ 86, 8055–8058 (1989). Article  CAS  Google Scholar  * Goedert, J. _et al_. Mother-to-infant transmission of human immunodeficiency virus type 1: Association with prematurity or low anti-gp!20. _Lancet_ 2, 1351–1354 (1989). Article  CAS  PubMed  Google Scholar  * Dubensky, T., Campell, B. & Villarreal, L. Direct transfection of viral and plasmid DNA into the liver of spleen of mice. _Proc. Natl. Acad. Sci. USA_ 81, 7529–7533 (1984). Article  CAS  PubMed  PubMed Central  Google Scholar  * Raz, E. _et al_. Systemic immunological effects of cytokine genes injected into skeletal muscle. _Proc. Natl. Acad. Sci. USA_ 90, 4523 (1993). Article  CAS  Google Scholar  * Wolff, J.A. _et al_. Direct gene transfer into mouse muscle _in vivo_. _Science_ 247, 1465–1468 (1990). Article  CAS  PubMed  Google Scholar  * Wang, B. _et al_. Immunization by direct DNA inoculation induces rejection of tumor cell challenge. _Hum. Gene Ther._ 6, 407–418 (1995). Article  CAS  PubMed  Google Scholar  * Ulmer, J.B. _et al_. Heterologous protection against influenza by injection of DNA encoding a viral protein. _Science_ 259, 1745–1749 (1993). Article  CAS  PubMed  Google Scholar  * Tang, D.C., Devit, M. & Johnston, S.A. Genetic immunization is a simple method for eliciting an immune response. _Nature_ 356, 152–154 (1992). Article  CAS  PubMed  Google Scholar  * Michel, M.L. _et al_. DNA-mediated immunization to the hepatitis B surface antigen in mice: Aspects of the humoral response mimic hepatitis B viral infection in humans. _Proc. Natl. Acad. Sci. USA_ 92, 5307–5311 (1995). Article  CAS  PubMed  PubMed Central  Google Scholar  * Lowrie, D.B., Tascon, R.E., Colston, M.J. & Silva, C.L. Towards a DNA vaccine against tuberculosis. _Vaccine_ 12, 1537–1540 (1994). Article  CAS  PubMed  Google Scholar  * Barry, M., Lai, W. & Johnston, S. Protection against mycoplasma infection using expression-library immunization. _Nature_ 377, 632–635 (1995). Article  CAS  PubMed  Google Scholar  * Fynan, E.F., Webster, R.G., Fuller, D.H. & Haynes, J.R. DNA vaccines: Protective immunizations by parental, mucosal and gene-gun inoculations. _Proc. Natl. Acad. Sci. USA_ 90, 11478–11482 (1993). Article  CAS  PubMed  PubMed Central  Google Scholar  * Wang, B. _et al_. DNA inoculation induces protective _in vivo_ immune responses against cellular challenge with HIV-1 antigen-expressing cells. _AIDS Res. Hum. Retroviruses_ 10 (Suppl. 2), S35–S41 (1994). Article  CAS  PubMed  Google Scholar  * Wang, B. _et al_. DNA Inoculation induces cross clade anti-HIV-1 responses. _Ann. NY Acad. Sci._ 772, 186–197 (1995). Article  CAS  PubMed  Google Scholar  * Wang, B. _et al_. Induction of humoral and cellular immune responses to the human immunodeficiency virus type 1 in non-human primates. _Virology_ 221, 102–112 (1995). Article  Google Scholar  * Wang, B. _et al_. Gene inoculation generates immune responses against human immunodeficiency virus type 1. _Proc. Natl. Acad. Sci. USA_ 90, 4156–4160 (1993) Article  CAS  PubMed  PubMed Central  Google Scholar  * Boyer, J.D. _et al_. _In vivo_ protective anti-HIV immune responses in non-human primates through DNA immunization. _J. Med. Primatol._ 25, 242–250 (1996). Article  CAS  PubMed  Google Scholar  * Lu, S., Santoro, J.C., Fuller, D.H., Haynes, J.R. & Robinson, H.L. Use of DNAs expressing HIV-1 envand non-infectious HIV-1 particles to raise antibody responses in mice. _Virology_ 209, 147–154 (1995). Article  CAS  PubMed  Google Scholar  * Haynes, J.R., Fuller, D.H., Eisenbraun, M.D., Ford, M.J., Pertmer, T.M. Accell→ particle-mediated DNA immunization elicits humoral, cytotoxic and protective responses. _AIDS Res. Hum. Retrovlruses_ 10 (Suppl. 2), S43–S45 (1994). Google Scholar  * Okuda, K. _et al_. Induction of potent humoral and cell-mediated immune responses following direct injection of DNA encoding the HIV type 1 _env_ and _rev_ gene products. _AIDS Res. Hum. Retroviruses_ 11, 933–943 (1995). Article  CAS  PubMed  Google Scholar  * Lu, S. _et al_. Simian Immunodeficiency virus DNA vaccine trial in macaques. _J. Virol._ 70, 3978–3991 (1996). CAS  PubMed  PubMed Central  Google Scholar  * Muster, T. _et al_. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. _Virol._ 11, 6642–6647 (1993). Google Scholar  * Vandamme, A.-M. Polymerase chain reaction (PCR) as a diagnostic tool in HIV infection. _Verh. K. Acad. Geneeskd. Belg._ 3, 231–265 (1994). Google Scholar  * Vandamme, A.-M. _et al_. Detection of HIV-1 RNA in plasma and serum samples using the NASBA amplification system compared to RNA-PCR. _J. Virol. Methods_ 52 121–132 (1995). Article  CAS  PubMed  Google Scholar  * Shibata, R. _et al_. Resistance of previously infected chimpanzees to successive challenges with a heterologous intraclade B strain of human immunodeficiency virus type 1. _J. Virol._ 70, 4361–4369 (1996). CAS  PubMed  PubMed Central  Google Scholar  * Lane, H.C., Depper, J.M., Greene, W.C., Whjalen, C., Waldmann, T.A. & Fauci, A.D. Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome: Evidence for a selective defect in soluble antigen recognition. _N. Engl. J. Med._ 313, 79–84 (1985). Article  CAS  PubMed  Google Scholar  * Gruters, R.A. _et al_. Selective loss of T cell functions in different stages of HIV infection, fur. _J. Immunol._ 20, 1038–1044 (1990). Google Scholar  * Vingerhoets, J.H. _et al_. Increased cytolytic T lymphocyte activity and decreased B7 responsiveness are associated with CD28 down-regulation on CD8+ T cells from HIV-infected subjects. _Clin. Exp. Immun._ 100, 425–433 (1995). Article  CAS  PubMed  PubMed Central  Google Scholar  * Levine, B.L. _et al_. Antiviral effect and ex vivo CD4 T cell proliferation in HIV-positive patients as a results of CD28 costimulation. _Science_ 272, 1939–1943 (1996). Article  CAS  PubMed  Google Scholar  * Brinchmann, J.E. _et al_. Expression of costimulatory molecule CD28 on T cells in human immunodeficiency virus type 1 infection: Functional and clinical correlations. _J. Infect. Dis._ 169, 730–738 (1993). Article  Google Scholar  * Ho, D.D. _et al_. Rapid turnover of plasma virions and CD4+ lymphocytes in HIV-1 infection. _Nature_ 373, 123–126 (1995). Article  CAS  PubMed  Google Scholar  * Wei, X. _et al_. Viral dynamics in human immunodeficiency virus type 1 infection. _Nature_ 373, 117–122 (1995). Article  CAS  PubMed  Google Scholar  * Montifiori, D.C., Robinson, W.E., Schiffmann, S.S. & Michell, W.M. Evaluation of antiviral drugs and neutralizing antibodies to human immunodeficiency virus by a rapid and sensitive microtiter infection assay. _J. Clin. Invest._ 6, 231–235 (1988). Google Scholar  Download references AUTHOR INFORMATION Author notes * Jean D. Boyer and Kenneth E. Ugen: These authors contributed equally to this manuscript. AUTHORS AND AFFILIATIONS * Department of Pathology and Laboratory Medicine, University of Pennsylvania, SOS Stellar-Chance Building, 422 Curie Boulevard, Philadelphia, Pennsylvania, 19104, USA Jean D. Boyer, Bin Wang, Michael Agadjanyan, Lori Gilbert, Michael Chattergoon & David B. Weiner * Department of Medical Microbiology and Immunology, University of South Florida, MDC10 12901 Bruce B. Downs Boulevard, Tampa, Florida, 33612, USA Kenneth E. Ugen * Department of Pediatrics, University of Pennsylvania, 505 Stellar-Chance Building, 422 Curie Boulevard, Philadelphia, Pennsylvania, 19104, USA Mark L. Bagarazzi * White Sands Research Center, Coulston Foundation, 1300 Lavelle Road, Alamogordo, New Mexico, 88310, USA Patrice Frost & Ali Javadian * Hospital of the University of Pennsylvania, 912 Stellar-Chance Building, 422 Curie Boulevard, Philadelphia, Pennsylvania, 19104, USA Williams V. Williams * Department of Pathology, Harvard University, LMRC-5, 221 Longwood Avenue, Boston, Massachusetts, 02115, USA Yosef Refaeli * Apollon Inc., 1 Great Valley Parkway, Malvern, Pennsylvania, 19355, USA Richard B. Ciccarelli, Daniel Mccallus & Leslie coney Authors * Jean D. Boyer View author publications You can also search for this author inPubMed Google Scholar * Kenneth E. Ugen View author publications You can also search for this author inPubMed Google Scholar * Bin Wang View author publications You can also search for this author inPubMed Google Scholar * Michael Agadjanyan View author publications You can also search for this author inPubMed Google Scholar * Lori Gilbert View author publications You can also search for this author inPubMed Google Scholar * Mark L. Bagarazzi View author publications You can also search for this author inPubMed Google Scholar * Michael Chattergoon View author publications You can also search for this author inPubMed Google Scholar * Patrice Frost View author publications You can also search for this author inPubMed Google Scholar * Ali Javadian View author publications You can also search for this author inPubMed Google Scholar * Williams V. Williams View author publications You can also search for this author inPubMed Google Scholar * Yosef Refaeli View author publications You can also search for this author inPubMed Google Scholar * Richard B. Ciccarelli View author publications You can also search for this author inPubMed Google Scholar * Daniel Mccallus View author publications You can also search for this author inPubMed Google Scholar * Leslie coney View author publications You can also search for this author inPubMed Google Scholar * David B. Weiner View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Boyer, J., Ugen, K., Wang, B. _et al._ Protection of chimpanzees from high-dose heterologous HIV-1 challenge by DNA vaccination. _Nat Med_ 3, 526–532 (1997). https://doi.org/10.1038/nm0597-526 Download citation * Received: 21 November 1996 * Accepted: 04 March 1997 * Issue Date: 01 May 1997 * DOI: https://doi.org/10.1038/nm0597-526 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

ABSTRACT Novel approaches for the generation of more effective vaccines for HIV-1 are of significant importance. In this report we analyze the immunogenicity and efficacy of an HIV-1 DNA


vaccine encoding _env, rev_ and _gag/pol_ in a chimpanzee model system. The immunized animals developed specific cellular and humoral immune responses. Animals were challenged with a


heterologous chimpanzee titered stock of HIV-1 SF2 virus and followed for 48 weeks after challenge. Polymerase chain reaction coupled with reverse transcription (RT-PCR) results indicated


infection in the control animal, whereas those animals vaccinated with the DNA constructs were protected from the establishment of infection. These studies serve as an important benchmark


for the use of DNA vaccine technology for the production of protective immune responses. Access through your institution Buy or subscribe This is a preview of subscription content, access


via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy


this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: *


Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS BOTH CHIMPANZEE ADENOVIRUS-VECTORED AND DNA VACCINES


INDUCED LONG-TERM IMMUNITY AGAINST NIPAH VIRUS INFECTION Article Open access 04 November 2023 HETEROLOGOUS VACCINATION REGIMENS WITH SELF-AMPLIFYING RNA AND ADENOVIRAL COVID VACCINES INDUCE


ROBUST IMMUNE RESPONSES IN MICE Article Open access 17 May 2021 INFECTIOUS RNA VACCINE PROTECTS MICE AGAINST CHIKUNGUNYA VIRUS INFECTION Article Open access 03 December 2020 REFERENCES *


Haynes, B.F., Pantaleo, C.,& Fauci, A.S. Toward an understanding of the correlates of protective immunity to HIV infection. _Science_ 271, 324–328 (1996). Article  CAS  PubMed  Google


Scholar  * Pantaleo, G. _et al_. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. _N. Engl. J. Med._ 332, 209–216 (1995). Article  CAS  PubMed 


Google Scholar  * Rinaldo, C. _et al_. High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of


disease in HIV-1 infected long-term nonprogressors. _J. Virol._ 69, 5838–5842 (1995). CAS  PubMed  PubMed Central  Google Scholar  * Rowland-Jones, S. _et al_. HIV-specific cytotoxic T-cells


in HIV-exposed but uninfected Gambian women. _Nature Med._ 1, 59–64 (1995). Article  PubMed  Google Scholar  * Rowland-Jones, S., Nixon, D. & Aldhous, M. HIV-specific cytotoxic T-cell


activity in an HIV-exposed but uninfected infant. _Lancet_ 341, 860–861 (1993). Article  CAS  PubMed  Google Scholar  * Ugen, K.E. _et al_. Verticaltransmissionofimmunodeficiency virus type


1: Seroreactivity by maternal antibodies to the carboxy region of the gp41 envelope. _J. Infect. Dis._ 175, 63–69 (1997). Article  CAS  PubMed  Google Scholar  * Ugen, K.E. _et al_. Vertical


transmission of human immunodeficiency virus (HIV) infection: Reactivity of maternal sera with glycoprotein 120 and 41 peptides from HIV type 1. _J. Clin. Invest._ 89, 1923–1930 (1992).


Article  CAS  PubMed  PubMed Central  Google Scholar  * Rossi, P. _et al_. Presence of maternal antibodies to human immunodeficiency virus 1 envelope glycoprotein gpl 20 epitopes correlates


with the uninfected status of children born to seropositive mothers. _Proc. Not. Acad. Sci. USA_ 86, 8055–8058 (1989). Article  CAS  Google Scholar  * Goedert, J. _et al_. Mother-to-infant


transmission of human immunodeficiency virus type 1: Association with prematurity or low anti-gp!20. _Lancet_ 2, 1351–1354 (1989). Article  CAS  PubMed  Google Scholar  * Dubensky, T.,


Campell, B. & Villarreal, L. Direct transfection of viral and plasmid DNA into the liver of spleen of mice. _Proc. Natl. Acad. Sci. USA_ 81, 7529–7533 (1984). Article  CAS  PubMed 


PubMed Central  Google Scholar  * Raz, E. _et al_. Systemic immunological effects of cytokine genes injected into skeletal muscle. _Proc. Natl. Acad. Sci. USA_ 90, 4523 (1993). Article  CAS


  Google Scholar  * Wolff, J.A. _et al_. Direct gene transfer into mouse muscle _in vivo_. _Science_ 247, 1465–1468 (1990). Article  CAS  PubMed  Google Scholar  * Wang, B. _et al_.


Immunization by direct DNA inoculation induces rejection of tumor cell challenge. _Hum. Gene Ther._ 6, 407–418 (1995). Article  CAS  PubMed  Google Scholar  * Ulmer, J.B. _et al_.


Heterologous protection against influenza by injection of DNA encoding a viral protein. _Science_ 259, 1745–1749 (1993). Article  CAS  PubMed  Google Scholar  * Tang, D.C., Devit, M. &


Johnston, S.A. Genetic immunization is a simple method for eliciting an immune response. _Nature_ 356, 152–154 (1992). Article  CAS  PubMed  Google Scholar  * Michel, M.L. _et al_.


DNA-mediated immunization to the hepatitis B surface antigen in mice: Aspects of the humoral response mimic hepatitis B viral infection in humans. _Proc. Natl. Acad. Sci. USA_ 92, 5307–5311


(1995). Article  CAS  PubMed  PubMed Central  Google Scholar  * Lowrie, D.B., Tascon, R.E., Colston, M.J. & Silva, C.L. Towards a DNA vaccine against tuberculosis. _Vaccine_ 12,


1537–1540 (1994). Article  CAS  PubMed  Google Scholar  * Barry, M., Lai, W. & Johnston, S. Protection against mycoplasma infection using expression-library immunization. _Nature_ 377,


632–635 (1995). Article  CAS  PubMed  Google Scholar  * Fynan, E.F., Webster, R.G., Fuller, D.H. & Haynes, J.R. DNA vaccines: Protective immunizations by parental, mucosal and gene-gun


inoculations. _Proc. Natl. Acad. Sci. USA_ 90, 11478–11482 (1993). Article  CAS  PubMed  PubMed Central  Google Scholar  * Wang, B. _et al_. DNA inoculation induces protective _in vivo_


immune responses against cellular challenge with HIV-1 antigen-expressing cells. _AIDS Res. Hum. Retroviruses_ 10 (Suppl. 2), S35–S41 (1994). Article  CAS  PubMed  Google Scholar  * Wang, B.


_et al_. DNA Inoculation induces cross clade anti-HIV-1 responses. _Ann. NY Acad. Sci._ 772, 186–197 (1995). Article  CAS  PubMed  Google Scholar  * Wang, B. _et al_. Induction of humoral


and cellular immune responses to the human immunodeficiency virus type 1 in non-human primates. _Virology_ 221, 102–112 (1995). Article  Google Scholar  * Wang, B. _et al_. Gene inoculation


generates immune responses against human immunodeficiency virus type 1. _Proc. Natl. Acad. Sci. USA_ 90, 4156–4160 (1993) Article  CAS  PubMed  PubMed Central  Google Scholar  * Boyer, J.D.


_et al_. _In vivo_ protective anti-HIV immune responses in non-human primates through DNA immunization. _J. Med. Primatol._ 25, 242–250 (1996). Article  CAS  PubMed  Google Scholar  * Lu,


S., Santoro, J.C., Fuller, D.H., Haynes, J.R. & Robinson, H.L. Use of DNAs expressing HIV-1 envand non-infectious HIV-1 particles to raise antibody responses in mice. _Virology_ 209,


147–154 (1995). Article  CAS  PubMed  Google Scholar  * Haynes, J.R., Fuller, D.H., Eisenbraun, M.D., Ford, M.J., Pertmer, T.M. Accell→ particle-mediated DNA immunization elicits humoral,


cytotoxic and protective responses. _AIDS Res. Hum. Retrovlruses_ 10 (Suppl. 2), S43–S45 (1994). Google Scholar  * Okuda, K. _et al_. Induction of potent humoral and cell-mediated immune


responses following direct injection of DNA encoding the HIV type 1 _env_ and _rev_ gene products. _AIDS Res. Hum. Retroviruses_ 11, 933–943 (1995). Article  CAS  PubMed  Google Scholar  *


Lu, S. _et al_. Simian Immunodeficiency virus DNA vaccine trial in macaques. _J. Virol._ 70, 3978–3991 (1996). CAS  PubMed  PubMed Central  Google Scholar  * Muster, T. _et al_. A conserved


neutralizing epitope on gp41 of human immunodeficiency virus type 1. _Virol._ 11, 6642–6647 (1993). Google Scholar  * Vandamme, A.-M. Polymerase chain reaction (PCR) as a diagnostic tool in


HIV infection. _Verh. K. Acad. Geneeskd. Belg._ 3, 231–265 (1994). Google Scholar  * Vandamme, A.-M. _et al_. Detection of HIV-1 RNA in plasma and serum samples using the NASBA amplification


system compared to RNA-PCR. _J. Virol. Methods_ 52 121–132 (1995). Article  CAS  PubMed  Google Scholar  * Shibata, R. _et al_. Resistance of previously infected chimpanzees to successive


challenges with a heterologous intraclade B strain of human immunodeficiency virus type 1. _J. Virol._ 70, 4361–4369 (1996). CAS  PubMed  PubMed Central  Google Scholar  * Lane, H.C.,


Depper, J.M., Greene, W.C., Whjalen, C., Waldmann, T.A. & Fauci, A.D. Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome: Evidence for a


selective defect in soluble antigen recognition. _N. Engl. J. Med._ 313, 79–84 (1985). Article  CAS  PubMed  Google Scholar  * Gruters, R.A. _et al_. Selective loss of T cell functions in


different stages of HIV infection, fur. _J. Immunol._ 20, 1038–1044 (1990). Google Scholar  * Vingerhoets, J.H. _et al_. Increased cytolytic T lymphocyte activity and decreased B7


responsiveness are associated with CD28 down-regulation on CD8+ T cells from HIV-infected subjects. _Clin. Exp. Immun._ 100, 425–433 (1995). Article  CAS  PubMed  PubMed Central  Google


Scholar  * Levine, B.L. _et al_. Antiviral effect and ex vivo CD4 T cell proliferation in HIV-positive patients as a results of CD28 costimulation. _Science_ 272, 1939–1943 (1996). Article 


CAS  PubMed  Google Scholar  * Brinchmann, J.E. _et al_. Expression of costimulatory molecule CD28 on T cells in human immunodeficiency virus type 1 infection: Functional and clinical


correlations. _J. Infect. Dis._ 169, 730–738 (1993). Article  Google Scholar  * Ho, D.D. _et al_. Rapid turnover of plasma virions and CD4+ lymphocytes in HIV-1 infection. _Nature_ 373,


123–126 (1995). Article  CAS  PubMed  Google Scholar  * Wei, X. _et al_. Viral dynamics in human immunodeficiency virus type 1 infection. _Nature_ 373, 117–122 (1995). Article  CAS  PubMed 


Google Scholar  * Montifiori, D.C., Robinson, W.E., Schiffmann, S.S. & Michell, W.M. Evaluation of antiviral drugs and neutralizing antibodies to human immunodeficiency virus by a rapid


and sensitive microtiter infection assay. _J. Clin. Invest._ 6, 231–235 (1988). Google Scholar  Download references AUTHOR INFORMATION Author notes * Jean D. Boyer and Kenneth E. Ugen: These


authors contributed equally to this manuscript. AUTHORS AND AFFILIATIONS * Department of Pathology and Laboratory Medicine, University of Pennsylvania, SOS Stellar-Chance Building, 422


Curie Boulevard, Philadelphia, Pennsylvania, 19104, USA Jean D. Boyer, Bin Wang, Michael Agadjanyan, Lori Gilbert, Michael Chattergoon & David B. Weiner * Department of Medical


Microbiology and Immunology, University of South Florida, MDC10 12901 Bruce B. Downs Boulevard, Tampa, Florida, 33612, USA Kenneth E. Ugen * Department of Pediatrics, University of


Pennsylvania, 505 Stellar-Chance Building, 422 Curie Boulevard, Philadelphia, Pennsylvania, 19104, USA Mark L. Bagarazzi * White Sands Research Center, Coulston Foundation, 1300 Lavelle


Road, Alamogordo, New Mexico, 88310, USA Patrice Frost & Ali Javadian * Hospital of the University of Pennsylvania, 912 Stellar-Chance Building, 422 Curie Boulevard, Philadelphia,


Pennsylvania, 19104, USA Williams V. Williams * Department of Pathology, Harvard University, LMRC-5, 221 Longwood Avenue, Boston, Massachusetts, 02115, USA Yosef Refaeli * Apollon Inc., 1


Great Valley Parkway, Malvern, Pennsylvania, 19355, USA Richard B. Ciccarelli, Daniel Mccallus & Leslie coney Authors * Jean D. Boyer View author publications You can also search for


this author inPubMed Google Scholar * Kenneth E. Ugen View author publications You can also search for this author inPubMed Google Scholar * Bin Wang View author publications You can also


search for this author inPubMed Google Scholar * Michael Agadjanyan View author publications You can also search for this author inPubMed Google Scholar * Lori Gilbert View author


publications You can also search for this author inPubMed Google Scholar * Mark L. Bagarazzi View author publications You can also search for this author inPubMed Google Scholar * Michael


Chattergoon View author publications You can also search for this author inPubMed Google Scholar * Patrice Frost View author publications You can also search for this author inPubMed Google


Scholar * Ali Javadian View author publications You can also search for this author inPubMed Google Scholar * Williams V. Williams View author publications You can also search for this


author inPubMed Google Scholar * Yosef Refaeli View author publications You can also search for this author inPubMed Google Scholar * Richard B. Ciccarelli View author publications You can


also search for this author inPubMed Google Scholar * Daniel Mccallus View author publications You can also search for this author inPubMed Google Scholar * Leslie coney View author


publications You can also search for this author inPubMed Google Scholar * David B. Weiner View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND


PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Boyer, J., Ugen, K., Wang, B. _et al._ Protection of chimpanzees from high-dose heterologous HIV-1 challenge by DNA


vaccination. _Nat Med_ 3, 526–532 (1997). https://doi.org/10.1038/nm0597-526 Download citation * Received: 21 November 1996 * Accepted: 04 March 1997 * Issue Date: 01 May 1997 * DOI:


https://doi.org/10.1038/nm0597-526 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently


available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative