Resistance to Infection, Early and Persistent Suppression of Simian Immunodeficiency Virus SIV<sub>mac251</sub>Viremia, and Significant Reduction of Tissue Viral Burden after Mucosal Vaccination in Female Rhesus Macaques

Manrique, Mariana; Kozlowski, Pamela A.; Cobo-Molinos, Antonio; Wang, Shainn Wei; Wilson, Robert L.; Viedma, Maria del Pilar Martinez; Montefiori, David C.; Carville, Angela; Aldovini, Anna

doi:10.1128/jvi.02523-13

Cited by 19 publications

(32 citation statements)

References 49 publications

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“…84,85 This vaccine, when delivered to the buccal mucosa of RMs, induced greater and more functionally diverse rectal IgA responses as compared to intranasally, intraintestinally, and intravaginally delivered vaccine, although the differences were not statistically significant. 84 This oral vaccine also generated equivalent vaginal IgA responses when compared to intravaginal administration, and overall induced IgA in multiple mucosal sites.…”

Section: Oral Vaccinationmentioning

confidence: 95%

“…When challenged intravaginally with repeated low dose SIV mac251 , intestinally vaccinated animals were reported to withstand a greater number of challenges before infection occurred. 85 On the other hand, after the animals became infected, the intestinal group was least protected from disease, and a greater degree of disease control was observed in orally and nasally vaccinated animals with 50% reaching undetectable levels of viremia. Moreover,…”

Section: Oral 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: Oral Vaccinationmentioning

confidence: 95%

Section: Oral 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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“…Several SIV vaccine studies in adult macaques have highlighted the importance of mucosal IgA in protection against SIV infection (15,20,(54)(55)(56)(57), but the role of IgA in vaccine-mediated protection against HIV acquisition remains unclear. The fact that plasma IgA responses in the RV144 trial were positively correlated with HIV infection risk does not negate the potential role of mucosal IgA in the protection of HIV acquisition.…”

Section: Figmentioning

confidence: 99%

“…Neutralizing activity was measured as described previously (19) using heat-inactivated plasma, TZM-bl cells (AIDS Reagent Program), and a clone of SIV mac251 (clone C) derived in the laboratory (GenBank accession number KT447167). This clone was deemed a tier 1 virus based on the finding that clone C neutralizing antibody titers in plasma of SIV-infected adult macaques were virtually identical to those previously measured in assays with an established tier 1 SIV mac251 (20).…”

Section: Animals Infant Rhesus Macaques (Macaca Mulatta)mentioning

confidence: 99%

Vaccine-Elicited Mucosal and Systemic Antibody Responses Are Associated with Reduced Simian Immunodeficiency Viremia in Infant Rhesus Macaques

Jensen

Nabi

Rompay

et al. 2016

J Virol

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Despite significant progress in reducing peripartum mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV)with antiretroviral therapy (ART), continued access to ART throughout the breastfeeding period is still a limiting factor, and breast milk exposure to HIV accounts for up to 44% of MTCT. As abstinence from breastfeeding is not recommended, alternative means are needed to prevent MTCT of HIV. We have previously shown that oral vaccination at birth with live attenuated Mycobacterium tuberculosis strains expressing simian immunodeficiency virus (SIV) genes safely induces persistent SIV-specific cellular and humoral immune responses both systemically and at the oral and intestinal mucosa. Here, we tested the ability of oral M. tuberculosis vaccine strains expressing SIV Env and Gag proteins, followed by systemic heterologous (MVA-SIV Env/Gag/Pol) boosting, to protect neonatal macaques against oral SIV challenge. While vaccination did not protect infant macaques against oral SIV acquisition, a subset of immunized animals had significantly lower peak viremia which inversely correlated with prechallenge SIV Env-specific salivary and intestinal IgA responses and higher-avidity SIV Env-specific IgG in plasma. These controller animals also maintained CD4؉ T cell populations better and showed reduced tissue pathology compared to noncontroller animals. We show that infants vaccinated at birth can

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“…The DNA prime and modified vaccinia virus Ankara (MVA) boost approach has been shown to induce a strong T cell and antibody response against simian immunodeficiency virus (SIV) and HIV in NHPs (12)(13)(14)(15)(16)(17)(18)(19)(20)(21), and DNA/MVA HIV-1 vaccines have been shown to be safe and highly immunogenic in people (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Our previous studies using DNA/MVA SIVmac239 immunogens showed a significant delay in the acquisition of intrarectal (i.r.)…”

mentioning

confidence: 99%

Human Immunodeficiency Virus C.1086 Envelope gp140 Protein Boosts following DNA/Modified Vaccinia Virus Ankara Vaccination Fail To Enhance Heterologous Anti-V1V2 Antibody Response and Protection against Clade C Simian-Human Immunodeficiency Virus Challenge

Styles

Gangadhara

Reddy

et al. 2019

J Virol

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The RV144 human immunodeficiency virus type 1 (HIV-1) vaccine trial showed a strong association between anti-gp70 V1V2 scaffold (V1V2) and anti-V2 hot spot peptide (V2 HS) antibody responses and reduced risk of HIV infection. Accordingly, a primary goal for HIV vaccines is to enhance the magnitude and breadth of V1V2 and V2 HS antibody responses in addition to neutralizing antibodies. Here, we tested the immunogenicity and efficacy of HIV-1 C.1086 gp140 boosts administered sequentially after priming with CD40L-adjuvanted DNA/simian-human immunodeficiency virus (SHIV) and boosting with modified vaccinia virus Ankara (MVA)-SHIV vaccines in rhesus macaques. The DNA/MVA vaccination induced robust vaccine-specific CD4 and CD8 T cell responses with a polyfunctional profile. Two gp140 booster immunizations induced very high levels (∼2 mg/ml) of gp140 binding antibodies in serum, with strong reactivity directed against the homologous (C.1086) V1V2, V2 HS, V3, and gp41 immunodominant (ID) proteins. However, the vaccine-induced antibody showed 10-fold (peak) and 32-fold (prechallenge) weaker binding to the challenge virus (SHIV1157ipd3N4) V1V2 and failed to bind to the challenge virus V2 HS due to a single amino acid change. Point mutations in the immunogen V2 HS to match the V2 HS in the challenge virus significantly diminished the binding of vaccine-elicited antibodies to membrane-anchored gp160. Both vaccines failed to protect from infection following repeated SHIV1157ipd3N4 intrarectal challenges. However, only the protein-boosted animals showed enhanced viral control. These results demonstrate that C.1086 gp140 protein immunizations administered following DNA/MVA vaccination do not significantly boost heterologous V1V2 and V2 HS responses and fail to enhance protection against heterologous SHIV challenge. IMPORTANCE HIV, the virus that causes AIDS, is responsible for millions of infections and deaths annually. Despite intense research for the past 25 years, there remains no safe and effective vaccine available. The significance of this work is in identifying the pros and cons of adding a protein boost to an already well-established DNA/MVA HIV vaccine that is currently being tested in the clinic. Characterizing the effects of the protein boost can allow researchers going forward to design vaccines that generate responses that will be more effective against HIV. Our results in rhesus macaques show that boosting with a specific HIV envelope protein does not significantly boost antibody responses that were identified as immune correlates of protection in a moderately successful RV144 HIV vaccine trial in humans and highlight the need for the development of improved HIV envelope immunogens.

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Resistance to Infection, Early and Persistent Suppression of Simian Immunodeficiency Virus SIV_mac251Viremia, and Significant Reduction of Tissue Viral Burden after Mucosal Vaccination in Female Rhesus Macaques

Cited by 19 publications

References 49 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

Vaccine-Elicited Mucosal and Systemic Antibody Responses Are Associated with Reduced Simian Immunodeficiency Viremia in Infant Rhesus Macaques

Human Immunodeficiency Virus C.1086 Envelope gp140 Protein Boosts following DNA/Modified Vaccinia Virus Ankara Vaccination Fail To Enhance Heterologous Anti-V1V2 Antibody Response and Protection against Clade C Simian-Human Immunodeficiency Virus Challenge

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Resistance to Infection, Early and Persistent Suppression of Simian Immunodeficiency Virus SIVmac251Viremia, and Significant Reduction of Tissue Viral Burden after Mucosal Vaccination in Female Rhesus Macaques

Cited by 19 publications

References 49 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

Vaccine-Elicited Mucosal and Systemic Antibody Responses Are Associated with Reduced Simian Immunodeficiency Viremia in Infant Rhesus Macaques

Human Immunodeficiency Virus C.1086 Envelope gp140 Protein Boosts following DNA/Modified Vaccinia Virus Ankara Vaccination Fail To Enhance Heterologous Anti-V1V2 Antibody Response and Protection against Clade C Simian-Human Immunodeficiency Virus Challenge

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Resistance to Infection, Early and Persistent Suppression of Simian Immunodeficiency Virus SIV_mac251Viremia, and Significant Reduction of Tissue Viral Burden after Mucosal Vaccination in Female Rhesus Macaques