Replicating Adenovirus-Simian Immunodeficiency Virus (SIV) Recombinant Priming and Envelope Protein Boosting Elicits Localized, Mucosal IgA Immunity in Rhesus Macaques Correlated with Delayed Acquisition following a Repeated Low-Dose Rectal SIV
            <sub>mac251</sub>
            Challenge

Xiao, Peng; Patterson, L. Jean; Kuate, Seraphin; Brocca-Cofano, Egidio; Thomas, M. Albert; Venzon, David; Zhao, Jun; DiPasquale, Janet; Fenizia, Claudio; Lee, Eun Mi; Kalisz, Irene; Kalyanaraman, Vaniambadi S.; Pal, Ranajit; Montefiori, David C.; Keele, Brandon F.; Robert-Guroff, Marjorie

doi:10.1128/jvi.06812-11

Cited by 93 publications

(131 citation statements)

References 56 publications

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“…58 An insightful mucosal vaccination study in macaques utilized an env/rev/gag recombinant Ad5 prime, administered sublingually, intranasally/intratracheally, intravaginally, or intrarectally followed by an intramuscular monophosphoryl lipid A (MPL)-adjuvanted gp120 protein boost. 59 In all groups, Env/Gag-specific CD4 and CD8 central memory T cell populations were induced in the blood, and were significantly larger than those in nonvaccinated animals. In the mucosa, there was similar evidence of Env-specific memory T cell populations induced following the two priming vaccinations and the first boost (28 weeks) among intranasal/intratracheal, sublingual, and intrarectal groups.…”

Section: Mucosal Vaccination Routes To Elicit Gi Mucosal Immune Respomentioning

confidence: 96%

“…Macaques primed with an SIV env/rev/gag recombinant Ad5 delivered intrarectally followed by an intramuscular gp120 boost exhibited the highest Env-specific T cell responses, both central and effector memory subtypes, in the rectum and jejunum as well as the greatest levels of IgA in their rectal, nasal, vaginal, and salivary secretions when compared to subjects primed via the sublingual, intranasal/intratracheal, or intravaginal routes. 59 Among vaccinated macaques, all but one individual became infected with SIV after nine cycles of a repeated lowdose intrarectal SIV mac251 challenge. This animal was a member of the intrarectal vaccine group and was notable for its comparatively high avidity responses, levels of Env-specific IgA at all of the mucosal sites surveyed, and Env-specific serum antibody titers.…”

Section: Intrarectal Vaccinationmentioning

confidence: 99%

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Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Poles

Alvarez²,

Hioe³

2014

AIDS Research and Human Retroviruses

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CD4+ T cells in the mucosa of the gastrointestinal (GI) tract are preferentially targeted and depleted by HIV. As such, the induction of an effective anti-HIV immune response in the mucosa of the GI tract-through vaccination-could protect this vulnerable population of cells. Mucosal vaccination provides a promising means of inducing robust humoral and cellular responses in the GI tract. Here we review data from the literature about the effectiveness of various mucosal vaccination routes-oral (intraintestinal/tonsilar/sublingual), intranasal, and intrarectal-with regard to the induction of immune responses mediated by cytotoxic T cells and antibodies in the GI mucosa, as well as protective efficacy in challenge models. We present data from the literature indicating that mucosal routes have the potential to effectively elicit GI mucosal immunity and protect against challenge. Given their capacity for the induction of anti-HIV immune responses in the GI mucosa, we propose that mucosal routes, including the nonconventional sublingual, tonsilar, and intrarectal routes, be considered for the delivery of the next generation HIV vaccines. However, further studies are necessary to determine the ideal vectors and vaccination regimens for these routes of immunization and to validate their efficacy in controlling HIV infection. HIV Epidemics and Treatment HIV infection has resulted in the death of millions since the early 1980s, and has been responsible for significant morbidity and decline in quality of life for millions more. Each year, an estimated 50,000 people are newly infected with the virus in the United States alone, adding to the 34 million currently living with the virus worldwide.

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Section: Mucosal Vaccination Routes To Elicit Gi Mucosal Immune Respomentioning

confidence: 96%

Section: Intrarectal Vaccinationmentioning

confidence: 99%

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Poles

Alvarez²,

Hioe³

2014

AIDS Research and Human Retroviruses

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“…Phase I clinical trials are under way with intranasal delivery of this HIV-1 candidate vaccine (17). The importance of mucosal IgA humoral responses is highlighted in humans by the detection of HIV-specific IgA in semen or vaginal wash samples collected from some cohorts of sex workers exposed to HIV type 1 (HIV-1) but seronegative, which has been interpreted as an indication that local IgA, induced by viral exposure, can protect during subsequent exposures by interacting with HIV-1 in mucosal secretions (24)(25)(26).…”

mentioning

confidence: 99%

“…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). In another study, RM were intranasally vaccinated with a virosome-coupled trimeric gp41 protein that failed to generate systemic antibodies but elicited IgA responses in the genital tract and prevented vaginal simian-human immunodeficiency virus (SHIV) transmission.…”

mentioning

confidence: 99%

“…It has been shown that replicating Ad-HIV/SIV recombinant prime/envelope protein boost is able to elicit broad cellular immunity and functional humoral responses in serum and mucosal sites. Different routes of mucosal immunization with Ad have been explored; these routes include sublingual, intranasal/intratracheal, vaginal, and rectal routes (24,(27)(28)(29). The administration of adenovirus type 5 (Ad5)-SIV recombinants by any of these mucosal routes resulted in highly effective priming of systemic immunity as well as mucosal cellular immune responses and mucosal antibody responses after envelope subunit boosts at multiple mucosal sites.…”

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confidence: 99%

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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

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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.

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Nonhuman Primate Models for HIV/AIDS Vaccine Development

et al. 2013

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The development of HIV vaccines has been hampered by the lack of an animal model that can accurately predict vaccine efficacy. Chimpanzees can be infected with HIV-1 but are not practical for research. However, several species of macaques are susceptible to the Simian Immunodeficiency Viruses (SIV) that causes a disease in macaques that closely mimics HIV in humans. Thus, macaque-SIV models of HIV infection have become a critical foundation for AIDS vaccine development. Here, we examine the multiple variables and considerations that must be taken into account to use this NHP model effectively. These include the species and subspecies of macaques, virus strain, dose and route of administration and macaque genetics including Major Histocompatibility Complex molecules that affect immune responses and other virus restriction factors. We illustrate how these NHP models can be used to carry out studies of immune responses in mucosal and other tissues than could not easily be performed on human volunteers. Futhermore macaques are an ideal model system to optimize adjuvants, test vaccine platforms, and identify correlates of protection that can advance the HIV vaccine field. We also illustrate techniques used to identify different macaque lymphocyte populations and review some poxvirus vaccine candidates that are in various stages of clinical trials. Understanding how to effectively use this valuable model will greatly increase the likelihood of finding a successful vaccine for HIV.

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Replicating Adenovirus-Simian Immunodeficiency Virus (SIV) Recombinant Priming and Envelope Protein Boosting Elicits Localized, Mucosal IgA Immunity in Rhesus Macaques Correlated with Delayed Acquisition following a Repeated Low-Dose Rectal SIV _mac251 Challenge

Cited by 93 publications

References 56 publications

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

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

Nonhuman Primate Models for HIV/AIDS Vaccine Development

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Replicating Adenovirus-Simian Immunodeficiency Virus (SIV) Recombinant Priming and Envelope Protein Boosting Elicits Localized, Mucosal IgA Immunity in Rhesus Macaques Correlated with Delayed Acquisition following a Repeated Low-Dose Rectal SIV mac251 Challenge

Cited by 93 publications

References 56 publications

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

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

Nonhuman Primate Models for HIV/AIDS Vaccine Development

Contact Info

Product

Resources

About

Replicating Adenovirus-Simian Immunodeficiency Virus (SIV) Recombinant Priming and Envelope Protein Boosting Elicits Localized, Mucosal IgA Immunity in Rhesus Macaques Correlated with Delayed Acquisition following a Repeated Low-Dose Rectal SIV _mac251 Challenge