Induction of Mucosal Protection against Primary, Heterologous Simian Immunodeficiency Virus by a DNA Vaccine
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| Published in: | Journal of Virology Vol. 76; no. 7; pp. 3309 - 3317 |
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| AbstractList | An effective vaccine against human immunodeficiency virus (HIV) should protect against mucosal transmission of genetically divergent isolates. As a safe alternative to live attenuated vaccines, the immunogenicity and protective efficacy of a DNA vaccine containing simian immunodeficiency virus (SIV) strain 17E-Fr (SIV/17E-Fr) gag-pol-env was analyzed in rhesus macaques. Significant levels of cytotoxic T lymphocytes (CTL), but low to undetectable serum antibody responses, were observed following multiple immunizations. SIV-specific mucosal antibodies and CTL were also detected in rectal washes and gut-associated lymphoid tissues, respectively. Vaccinated and naive control monkeys were challenged intrarectally with SIV strain DeltaB670 (SIV/DeltaB670), a primary isolate whose env is 15% dissimilar to that of the vaccine strain. Four of seven vaccinees were protected from infection as determined by the inability to identify viral RNA or DNA sequences in the peripheral blood and the absence of anamnestic antibody responses postchallenge. This is the first report of mucosal protection against a primary pathogenic, heterologous isolate of SIV by using a commercially viable vaccine approach. These results support further development of a DNA vaccine for protection against HIV. An effective vaccine against human immunodeficiency virus (HIV) should protect against mucosal transmission of genetically divergent isolates. As a safe alternative to live attenuated vaccines, the immunogenicity and protective efficacy of a DNA vaccine containing simian immunodeficiency virus (SIV) strain 17E-Fr (SIV/17E-Fr) gag-pol-env was analyzed in rhesus macaques. Significant levels of cytotoxic T lymphocytes (CTL), but low to undetectable serum antibody responses, were observed following multiple immunizations. SIV-specific mucosal antibodies and CTL were also detected in rectal washes and gut-associated lymphoid tissues, respectively. Vaccinated and naive control monkeys were challenged intrarectally with SIV strain DeltaB670 (SIV/DeltaB670), a primary isolate whose env is 15% dissimilar to that of the vaccine strain. Four of seven vaccinees were protected from infection as determined by the inability to identify viral RNA or DNA sequences in the peripheral blood and the absence of anamnestic antibody responses postchallenge. This is the first report of mucosal protection against a primary pathogenic, heterologous isolate of SIV by using a commercially viable vaccine approach. These results support further development of a DNA vaccine for protection against HIV. Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology. For an alternate route to JVI .asm.org, visit: JVI |
| Author | Lawrence A. Wilson Tim Shipley Mary S. Wu Deborah Heydenburg Fuller Charles R. Rinaldo Premeela A. Rajakumar Kathleen Weis Joel R. Haynes Michael Murphey-Corb James T. Fuller Anita M. Trichel |
| AuthorAffiliation | PowderJect Vaccines, Inc., Madison, Wisconsin 53711, 1 University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, 2 Tulane Regional Primate Research Center, Covington, Louisiana 70433 3 |
| AuthorAffiliation_xml | – name: PowderJect Vaccines, Inc., Madison, Wisconsin 53711, 1 University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, 2 Tulane Regional Primate Research Center, Covington, Louisiana 70433 3 |
| Author_xml | – sequence: 1 givenname: Deborah Heydenburg surname: Fuller fullname: Fuller, Deborah Heydenburg organization: PowderJect Vaccines, Inc., Madison, Wisconsin 53711, USA – sequence: 2 givenname: Premeela A surname: Rajakumar fullname: Rajakumar, Premeela A – sequence: 3 givenname: Lawrence A surname: Wilson fullname: Wilson, Lawrence A – sequence: 4 givenname: Anita M surname: Trichel fullname: Trichel, Anita M – sequence: 5 givenname: James T surname: Fuller fullname: Fuller, James T – sequence: 6 givenname: Tim surname: Shipley fullname: Shipley, Tim – sequence: 7 givenname: Mary S surname: Wu fullname: Wu, Mary S – sequence: 8 givenname: Kathleen surname: Weis fullname: Weis, Kathleen – sequence: 9 givenname: Charles R surname: Rinaldo fullname: Rinaldo, Charles R – sequence: 10 givenname: Joel R surname: Haynes fullname: Haynes, Joel R – sequence: 11 givenname: Michael surname: Murphey-Corb fullname: Murphey-Corb, Michael |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/11884556$$D View this record in MEDLINE/PubMed |
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| Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Corresponding author. Mailing address: University of Pittsburgh School of Medicine, Department of Molecular Genetics and Biochemistry, Room E1240 Biomedical Science Tower, Pittsburgh, PA 15261. Phone: (412) 648-9462. Fax: (412) 648-1448. E-mail: mcorb@pitt.edu. |
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Mendeley... An effective vaccine against human immunodeficiency virus (HIV) should protect against mucosal transmission of genetically divergent isolates. As a safe... |
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| SubjectTerms | Amino Acid Sequence Animals Antibodies, Viral - analysis Gene Products, env - genetics HIV Envelope Protein gp120 - chemistry HIV Envelope Protein gp120 - genetics Human immunodeficiency virus Immunity, Mucosal Immunoglobulin A - analysis Immunoglobulin G - analysis Intestines - immunology Lymphoid Tissue - immunology Macaca mulatta Membrane Glycoproteins Molecular Sequence Data Rectum - immunology SAIDS Vaccines - administration & dosage Sequence Alignment Simian Acquired Immunodeficiency Syndrome - prevention & control Simian immunodeficiency virus Simian Immunodeficiency Virus - genetics Simian Immunodeficiency Virus - immunology T-Lymphocytes, Cytotoxic - immunology Vaccination Vaccines and Antiviral Agents Vaccines, DNA - administration & dosage Viral Envelope Proteins |
| Title | Induction of Mucosal Protection against Primary, Heterologous Simian Immunodeficiency Virus by a DNA Vaccine |
| URI | http://jvi.asm.org/content/76/7/3309.abstract https://www.ncbi.nlm.nih.gov/pubmed/11884556 https://search.proquest.com/docview/18278540 https://pubmed.ncbi.nlm.nih.gov/PMC136011 |
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