scholarly journals High Doses of GM-CSF Inhibit Antibody Responses in Rectal Secretions and Diminish Modified Vaccinia Ankara/Simian Immunodeficiency Virus Vaccine Protection in TRIM5α-Restrictive Macaques

2016 ◽  
Vol 197 (9) ◽  
pp. 3586-3596 ◽  
Author(s):  
Sunil Kannanganat ◽  
Linda S. Wyatt ◽  
Sailaja Gangadhara ◽  
Venkatesarlu Chamcha ◽  
Lynette S. Chea ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Virus Vaccine ◽  
Antibody Responses ◽  
Vaccine Protection ◽  
Gm Csf ◽  
Immunodeficiency Virus ◽  
High Doses ◽  
Inhibit Antibody

scholarly journals Breakthrough of SIV strain smE660 challenge in SIV strain mac239-vaccinated rhesus macaques despite potent autologous neutralizing antibody responses

2015 ◽  
Vol 112 (34) ◽  
pp. 10780-10785 ◽  
Author(s):  
Samantha L. Burton ◽  
Katie M. Kilgore ◽  
S. Abigail Smith ◽  
Sharmila Reddy ◽  
Eric Hunter ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Active Immunization ◽  
Antibody Responses ◽  
Challenge Virus ◽  
Gm Csf ◽  
Immunodeficiency Virus

Although the correlates of immunological protection from human immunodeficiency virus or simian immunodeficiency virus infection remain incompletely understood, it is generally believed that medium to high titers of serum neutralizing antibodies (nAbs) against the challenge virus will prevent infection. This paradigm is based on a series of studies in which passive transfer of HIV-specific nAbs protected rhesus macaques (RMs) from subsequent mucosal challenge with a chimeric human/simian immunodeficiency virus. However, it is unknown whether nAb titers define protection in the setting of active immunization. Here we determined serum nAb titers against breakthrough transmitted/founder (T/F) SIVsmE660-derived envelope glycoprotein (Env) variants from 14 RMs immunized with SIVmac239-based DNA-prime/modified vaccinia virus Ankara-boost vaccine regimens that included GM-CSF or CD40L adjuvants and conferred significant but incomplete protection against repeated low-dose intrarectal challenge. A single Env variant established infection in all RMs except one, with no identifiable genetic signature associated with vaccination breakthrough compared with T/F Envs from four unvaccinated monkeys. Breakthrough T/F Env pseudoviruses were potently neutralized in vitro by heterologous pooled serum from chronically SIVsmE660-infected monkeys at IC50 titers exceeding 1:1,000,000. Remarkably, the T/F Env pseudoviruses from 13 of 14 monkeys were also susceptible to neutralization by autologous prechallenge serum at in vitro IC50 titers ranging from 1:742–1:10,832. These titers were similar to those observed in vaccinated RMs that remained uninfected. These data suggest that the relationship between serum nAb titers and protection from mucosal SIV challenge in the setting of active immunization is more complex than previously recognized, warranting further studies into the balance between immune activation, target cell availability, and protective antibody responses.

scholarly journals Induction of Mucosal Protection against Primary, Heterologous Simian Immunodeficiency Virus by a DNA Vaccine

2002 ◽  
Vol 76 (7) ◽  
pp. 3309-3317 ◽  
Author(s):  
Deborah Heydenburg Fuller ◽  
Premeela A. Rajakumar ◽  
Lawrence A. Wilson ◽  
Anita M. Trichel ◽  
James T. Fuller ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Dna Vaccine ◽  
Dna Sequences ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Effective Vaccine ◽  
Lymphoid Tissues ◽  
Mucosal Protection ◽  
Mucosal Transmission ◽  
Immunodeficiency Virus

ABSTRACT 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.

scholarly journals Enhanced T- and B-cell responses to simian immunodeficiency virus (SIV)agm, SIVmac and human immunodeficiency virus type 1 Gag DNA immunization and identification of novel T-cell epitopes in mice via codon optimization

2009 ◽  
Vol 90 (10) ◽  
pp. 2513-2518 ◽  
Author(s):  
Christine S. Siegismund ◽  
Oliver Hohn ◽  
Reinhard Kurth ◽  
Stephen Norley
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
B Cell ◽  
Simian Immunodeficiency Virus ◽  
Codon Optimization ◽  
T Cell Epitopes ◽  
Gm Csf ◽  
Cell Responses ◽  
Immunodeficiency Virus

As a prelude to primate studies, the immunogenicity of wild-type and codon-optimized versions of simian immunodeficiency virus (SIV)agm Gag DNA, with and without co-administered granulocyte–macrophage colony-stimulating factor (GM-CSF) DNA, was directly compared in two strains of mice. Gag-specific T cells in the splenocytes of BALB/c and C57BL/6 mice immunized by gene gun were quantified by ELISpot using panels of overlapping synthetic peptides (15mers) spanning the entire capsid proteins of SIVagm, SIVmac and human immunodeficiency virus type 1. Specific antibodies were measured by ELISA. Codon optimization was shown to significantly increase the immune response to the DNA immunogens, reducing the amount of DNA necessary to induce cellular and antibody responses by one and two orders of magnitude, respectively. Co-administration of murine GM-CSF DNA was necessary for the induction of high level T- and B-cell responses. Finally, it was possible to identify both known and novel T-cell epitopes in the Gag proteins of the three viruses.

scholarly journals T-cell subset differentiation and antibody responses following antiretroviral therapy during simian immunodeficiency virus infection

Immunology ◽  
2018 ◽  
Vol 155 (4) ◽  
pp. 458-466
Author(s):  
Mitra Bhattacharyya ◽  
James B. Whitney ◽  
Michael Seaman ◽  
Dan H. Barouch ◽  
Pablo Penaloza-MacMaster
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Virus Infection ◽  
Simian Immunodeficiency Virus ◽  
Cell Subset ◽  
Antibody Responses ◽  
Simian Immunodeficiency Virus Infection ◽  
T Cell Subset ◽  
Immunodeficiency Virus

scholarly journals Immunization with a Live, Attenuated Simian Immunodeficiency Virus Vaccine Leads to Restriction of Viral Diversity in Rhesus Macaques Not Protected from Pathogenic Challenge

1999 ◽  
Vol 73 (5) ◽  
pp. 4443-4446 ◽  
Author(s):  
Donald L. Sodora ◽  
Kristine E. Sheridan ◽  
Preston A. Marx ◽  
Ruth I. Connor
Keyword(s):  
Genetic Diversity ◽  
Simian Immunodeficiency Virus ◽  
Virus Vaccine ◽  
Rhesus Macaques ◽  
Biological Characteristics ◽  
Viral Diversity ◽  
Immunodeficiency Virus ◽  
Sivmac251 Challenge ◽  
Selection Of

ABSTRACT Rhesus macaques immunized with simian immunodeficiency virus SIVmac239Δnef but not protected from SIVmac251 challenge were studied to determine the genetic and biological characteristics of the breakthrough viruses. Assessment of SIV genetic diversity (env V1-V2) revealed a reduction in the number of viral species in the immunized, unprotected macaques, compared to the number in nonimmunized controls. However, no evidence for selection of a specific V1-V2 genotype was observed, and biologically cloned isolates from the animals with breakthrough virus were similar with respect to replication kinetics and coreceptor use in vitro.

scholarly journals GM-CSF DNA: An adjuvant for higher avidity IgG, rectal IgA, and increased protection against the acute phase of a SHIV-89.6P challenge by a DNA/MVA immunodeficiency virus vaccine

Virology ◽  
2007 ◽  
Vol 369 (1) ◽  
pp. 153-167 ◽  
Author(s):  
Lilin Lai ◽  
Dalma Vödrös ◽  
Pamela A. Kozlowski ◽  
David C. Montefiori ◽  
Robert L. Wilson ◽  
...  
Keyword(s):  
Acute Phase ◽  
Virus Vaccine ◽  
Gm Csf ◽  
Immunodeficiency Virus

scholarly journals Protective Immune Responses Elicited by Deglycosylated Live-Attenuated Simian Immunodeficiency Virus Vaccine Are Associated with IL-15 Effector Functions

2020 ◽  
Vol 205 (5) ◽  
pp. 1331-1344
Author(s):  
Satoru Watanabe ◽  
Masayuki Fujino ◽  
Yohei Saito ◽  
Nursarat Ahmed ◽  
Hirotaka Sato ◽  
...  
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Virus Vaccine ◽  
Effector Functions ◽  
Immunodeficiency Virus
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