Long-Term Control of Simian Immunodeficiency Virusmac251 Viremia to Undetectable Levels in Half of Infected Female Rhesus Macaques Nasally Vaccinated with Simian Immunodeficiency Virus DNA/Recombinant Modified Vaccinia Virus Ankara

Manrique, Mariana; Kozlowski, Pamela A.; Cobo-Molinos, Antonio; Wang, Shainn Wei; Wilson, Robert L.; Montefiori, David C.; Mansfield, Keith G.; Carville, Angela; Aldovini, Anna

doi:10.4049/jimmunol.1002594

Cited by 32 publications

(46 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ϩ , and CD8 ϩ T-cell levels correlated with delayed progression to AIDS (22). These responses were also detected in this study and were more significant in the blood and rectal and vaginal mucosa of orally vaccinated animals, being detected at lower levels in the others.…”

Section: Discussionsupporting

confidence: 60%

“…In our previous nasal immunization studies with pVacc6 DNA and SIV MVA, systemic IgG responses were not induced (21,22). In this study, plasma anti-SIV IgG antibody concentration increased after particle immunization against Gag/Pol antigens in one animal vaccinated intestinally, four animals vaccinated nasally, and two animals vaccinated vaginally ( Fig.…”

Section: Methodsmentioning

confidence: 64%

“…To determine the most efficient mucosal route of immunization to stimulate the most diverse vaccine-induced immunity at different mucosal and systemic sites with the potential to protect rhesus macaques from SIV infection or to delay disease progression, four groups, each with seven female rhesus macaques, were vaccinated with 3 doses of SIV/cytokine DNAs in liposomes on day 1, week 8, and week 24, followed by one dose of SIV Gag/Pol/Env rMVA on week 32, previously tested in male and female animals (21,22). On week 48 and 50, all animals were boosted with 2,2=-dithiodipyridine (aldrithol-2 [AT-2])-inactivated SIVmac239 particles equivalent to 50 g of p28 CA (35).…”

Section: Methodsmentioning

confidence: 99%

“…and provided better protection from disease progression (21). Intranasal immunization with the same vaccine was able to protect from disease progression in female RM following vaginal challenge with SIVmac251 (22). SIV-specific CD4 ϩ and CD8 ϩ gamma interferon (IFN-␥)-producing T cells present at the time of challenge correlated with the subsequent control of the viremia and longer survival of these animals.…”

mentioning

confidence: 96%

“…SIV-specific CD4 ϩ and CD8 ϩ gamma interferon (IFN-␥)-producing T cells present at the time of challenge correlated with the subsequent control of the viremia and longer survival of these animals. This nasal DNA/rMVA vaccine did not stimulate significant humoral responses systemically or in vaginal mucosa (22). Modifications to stimulate greater mucosal antibody responses may further enhance the efficacy of this vaccine, as others have correlated vaccine-mediated induction of SIV-specific mucosal IgA at sites of viral challenge in nonhuman primates (NHP) with sterile protection, delayed acquisition of infection, or reduced viral loads after infection (23,24).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Immunogenicity of a Vaccine Regimen Composed of Simian Immunodeficiency Virus DNA, rMVA, and Viral Particles Administered to Female Rhesus Macaques via Four Different Mucosal Routes

Manrique

Kozlowski

Cobo-Molinos

et al. 2013

J Virol

Self Cite

View full text Add to dashboard Cite

A comparative evaluation of the immunity stimulated with a vaccine regimen that includes simian immunodeficiency virus (SIV), interleukin 2 (IL-2), and IL-15 DNAs, recombinant modified vaccinia virus Ankara (rMVA), and inactivated SIVmac239 particles administered into the oral and nasal cavities, small intestine, and vagina was carried out in female rhesus macaques to determine the best route to induce diverse anti-SIV immunity that may be critical to protection from SIV infection and disease. All four immunizations generated mucosal SIV-specific IgA. Oral immunization was as effective as vaginal immunization in inducing SIV-specific IgA in vaginal secretions and generated greater IgA responses in rectal secretions and saliva samples compared to the other immunization routes. All four immunizations stimulated systemic T-cell responses against Gag and Env, albeit to a different extent, with oral immunization providing greater magnitude and nasal immunization providing wider functional heterogeneity. SIV-specific T cells producing gamma interferon (IFN-␥) dominated these responses. Limited levels of SIV-specific IgG antibodies were detected in plasma samples, and no SIV-specific IgG antibodies were detected in secretions. Vaccination also induced CD4؉ and CD8 ؉ T-cell responses in the rectal and vaginal mucosa with greater functional heterogeneity than in blood samples. Rectal T-cell responses were significantly greater in the orally vaccinated animals than in the other animals. The most balanced, diverse, and higher-magnitude vaginal T-cell responses were observed after intestinal vaccination. Significantly higher CD8؉ granzyme B-positive T-cell responses were observed systemically after intestinal vaccination and in rectal cells after oral immunization. The majority of SIV-specific T cells that produced granzyme B did not produce cytokines. Of the immunization routes tested, oral vaccination provided the most diverse and significant response to the vaccine.

show abstract

Section: Discussionsupporting

confidence: 60%

Section: Methodsmentioning

confidence: 64%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 96%

mentioning

confidence: 99%

See 3 more Smart Citations

Immunogenicity of a Vaccine Regimen Composed of Simian Immunodeficiency Virus DNA, rMVA, and Viral Particles Administered to Female Rhesus Macaques via Four Different Mucosal Routes

Manrique

Kozlowski

Cobo-Molinos

et al. 2013

J Virol

Self Cite

View full text Add to dashboard Cite

show abstract

‘Omics Investigations of HIV and SIV Pathogenesis and Innate Immunity

Palermo

Fuller

2012

Current Topics in Microbiology and Immunology

View full text Add to dashboard Cite

In the 30 years since the advent of the AIDS epidemic, the biomedical community has put forward a battery of molecular therapies that are based on the accumulated knowledge of a limited number of viral targets. Despite these accomplishments, the community still confronts unanswered foundational questions about HIV infection. What are the cellular or biomolecular processes behind HIV pathogenesis? Can we elucidate the characteristics that distinguish those individuals who are naturally resistant to either infection or disease progression? The discovery of simian immunodeficiency viruses (SIVs) and the ensuing development of in vivo, nonhuman primate (NHP) infection models was a tremendous advance, especially in abetting the exploration of vaccine strategies. And while there have been numerous NHP infection models and vaccine trials performed, fundamental questions remain regarding host-virus interactions and immune correlates of protection. These issues are, perhaps, most starkly illustrated with the appreciation that many species of African nonhuman primates are naturally infected with strains of SIV that do not cause any appreciable disease while replicating to viral loads that match or exceed those seen with pathogenic SIV infections in Asian species of nonhuman primates. The last decade has seen the establishment of high-throughput molecular profiling tools, such as microarrays for transcriptomics, SNP arrays for genome features, and LC-MS techniques for proteins or metabolites. These provide the capacity to interrogate a biological model at a comprehensive, systems level, in contrast to historical approaches that characterized a few genes or proteins in an experiment. These methods have already had revolutionary impacts in understanding human diseases originating within the host genome such as genetic disorders and cancer, and the methods are finding increasing application in the context of infectious disease. We will provide a review of the use of such 'omics investigations as applied to understanding of HIV pathogenesis and innate immunity, drawing from our own research as well as the literature examples that utilized in vitro cell-based models or studies in nonhuman primates. We will also discuss the potential for systems biology to help guide strategies for HIV vaccines that offer significant protection by either preventing acquisition or strongly suppressing viral replication levels post-infection.

show abstract

Innate endogenous adjuvants prime to desirable immune responses via mucosal routes

Wang

Meng

2014

Protein Cell

View full text Add to dashboard Cite

Vaccination is an effective strategy to prevent infectious or immune related diseases, which has made remarkable contribution in human history. Recently increasing attentions have been paid to mucosal vaccination due to its multiple advantages over conventional ways. Subunit or peptide antigens are more reasonable immunogens for mucosal vaccination than live or attenuated pathogens, however adjuvants are required to augment the immune responses. Many mucosal adjuvants have been developed to prime desirable immune responses to different etiologies. Compared with pathogen derived adjuvants, innate endogenous molecules incorporated into mucosal vaccines demonstrate prominent adjuvanticity and safety. Nowadays, cytokines are broadly used as mucosal adjuvants for participation of signal transduction of immune responses, activation of innate immunity and polarization of adaptive immunity. Desired immune responses are promptly and efficaciously primed on basis of specific interactions between cytokines and corresponding receptors. In addition, some other innate molecules are also identified as potent mucosal adjuvants. This review focuses on innate endogenous mucosal adjuvants, hoping to shed light on the development of mucosal vaccines.

show abstract

Long-Term Control of Simian Immunodeficiency Virusmac251 Viremia to Undetectable Levels in Half of Infected Female Rhesus Macaques Nasally Vaccinated with Simian Immunodeficiency Virus DNA/Recombinant Modified Vaccinia Virus Ankara

Cited by 32 publications

References 57 publications

Immunogenicity of a Vaccine Regimen Composed of Simian Immunodeficiency Virus DNA, rMVA, and Viral Particles Administered to Female Rhesus Macaques via Four Different Mucosal Routes

Immunogenicity of a Vaccine Regimen Composed of Simian Immunodeficiency Virus DNA, rMVA, and Viral Particles Administered to Female Rhesus Macaques via Four Different Mucosal Routes

‘Omics Investigations of HIV and SIV Pathogenesis and Innate Immunity

Innate endogenous adjuvants prime to desirable immune responses via mucosal routes

Contact Info

Product

Resources

About