Protection of macaques against vaginal SHIV challenge by systemic or mucosal and systemic vaccinations with HIV-envelope

Barnett, Susan W.; Srivastava, Indresh K.; Kan, Elaine; Zhou, Fengmin; Goodsell, Amanda; Cristillo, Anthony D.; Ferrai, Maria Grazia; Weiss, Deborah; Letvin, Norman L.; Montefiori, David C.; Pal, Ranajit; Vajdy, Michael

doi:10.1097/qad.0b013e3282f3ca57

Cited by 107 publications

(105 citation statements)

References 46 publications

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“…The vaginal mucosa had particularly high frequencies of antigen-specific CD8 ϩ T cells following vaccine administration by both routes, possibly as a result of lymphocyte migration. This phenomenon previously has been shown using a variety of vaccine modalities and administration routes (2,26). The induction of cellular responses in the vaginal mucosa is consistent with the mucosal compartmentalization model that links immune induction in the respiratory and vaginal mucosa (22,28).…”

Section: Fig 9 Effect Of the Route Of Immunization On Pulmonary Cd8supporting

confidence: 57%

Efficient Generation of Mucosal and Systemic Antigen-Specific CD8⁺T-Cell Responses following Pulmonary DNA Immunization

Bivas-Benita

Bar

Gillard

et al. 2010

J Virol

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Although mucosal CD8؉ T-cell responses are important in combating mucosal infections, the generation of such immune responses by vaccination remains problematic. In the present study, we evaluated the ability of plasmid DNA to induce local and systemic antigen-specific CD8 ؉ T-cell responses after pulmonary administration. We show that the pulmonary delivery of plasmid DNA formulated with polyethyleneimine (PEI-DNA) induced robust systemic CD8 ؉ T-cell responses that were comparable in magnitude to those generated by intramuscular (i.m.) immunization. Most importantly, we observed that the pulmonary delivery of PEI-DNA elicited a 10-fold-greater antigen-specific CD8؉ T-cell response in lungs and draining lymph nodes of mice than that of i.m. immunization. The functional evaluation of these pulmonary CD8؉ T cells revealed that they produced type I cytokines, and pulmonary immunization with PEI-DNA induced lung-associated antigen-specific CD4 ؉ T cells that produced higher levels of interleukin-2 than those induced by i.m. immunization. Pulmonary PEI-DNA immunization also induced CD8 ؉ T-cell responses in the gut and vaginal mucosa. Finally, pulmonary, but not i.m., plasmid DNA vaccination protected mice from a lethal recombinant vaccinia virus challenge. These findings suggest that pulmonary PEI-DNA immunization might be a useful approach for immunizing against pulmonary pathogens and might also protect against infections initiated at other mucosal sites. Since establishing that antigen-specific CD8ϩ T-cell populations in mucosal sites may confer protection against intracellular pathogens that initiate infections at mucosal surfaces, vaccine strategies have been explored for eliciting cellular immune responses in mucosal tissues (40). Studies have been done to evaluate the immunogenicity of vaccines delivered to a variety of mucosal surfaces, including those of the nose, intestine, rectum, and vagina. These studies have shown that immunization at mucosal sites can induce larger numbers of antigen-specific CD8 ϩ T cells in mucosal tissues than parenteral immunization (3).Particular attention has focused on the lungs as a target for mucosal immunization. The lungs are an important mucosal portal of entry for pathogens. They are also a readily accessed mucosal site for the delivery of immunogens that might induce diverse mucosal immune responses. Pulmonary immunization strategies have been shown to generate potent Th1 responses and protective immunity against respiratory challenge with pathogens in several animal models (4,29,32,37,38).Because of the ease of generating vaccine constructs and the ability to administer repeated inoculations of the same vector, DNA immunization remains a promising vaccination strategy for eliciting cellular immune responses. Only a limited number of studies have been done to evaluate the immunogenicity of DNA vaccines following pulmonary delivery (4, 32). Although the importance of CD8 ϩ T lymphocytes in eradicating mucosal infections has been well established, it has not been determin...

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Section: Fig 9 Effect Of the Route Of Immunization On Pulmonary Cd8supporting

confidence: 57%

Efficient Generation of Mucosal and Systemic Antigen-Specific CD8⁺T-Cell Responses following Pulmonary DNA Immunization

Bivas-Benita

Bar

Gillard

et al. 2010

J Virol

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“…Passive immunization studies using neutralizing mAbs in nonhuman primates have established unequivocally that antibodies can block infection with simian human immunodeficiency viruses (SHIVs) (100)(101)(102)(103). Surprisingly, aside from homologous challenges where Env vaccines and SHIV Env proteins are matched (104,105), it has been difficult to correlate comparable vaccine-elicited neutralizing antibody titers with protection against SHIV where the Env protein is heterologous to the vaccine (82,106). The principal difference between the two approaches is that passive immunization is carried out against a "clean" background, devoid of ongoing host responses elicited by vaccination.…”

Section: Strategies To Elicit Continuous Protection Against Hiv By Vamentioning

confidence: 99%

Antibody persistence and T-cell balance: Two key factors confronting HIV vaccine development

Lewis

DeVico

Gallo

2014

Proc. Natl. Acad. Sci. U.S.A.

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The quest for a prophylactic AIDS vaccine is ongoing, but it is now clear that the successful vaccine must elicit protective antibody responses. Accordingly, intense efforts are underway to identify immunogens that elicit these responses. Regardless of the mechanism of antibodymediated protection, be it neutralization, Fc-mediated effector function, or both, antibody persistence and appropriate T-cell help are significant problems confronting the development of a successful AIDS vaccine. Here, we discuss the evidence illustrating the poor persistence of antibody responses to Env, the envelope glycoprotein of HIV-1, and the related problem of CD4 + T-cell responses that compromise vaccine efficacy by creating excess cellular targets of HIV-1 infection. Finally, we propose solutions to both problems that are applicable to all Envbased AIDS vaccines regardless of the mechanism of antibody-mediated protection.

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“…[63][64][65] Systemic vaccination followed by continued mucosal exposures in the presence of PrEP that is sufficient to prevent established infection may allow more effective development of mucosal response. The possibility of a detrimental interaction between ARV for prevention and vaccination has not yet been assessed.…”

Section: Mucosal Exposure In the Absence Of Chronic Infection Can Indmentioning

confidence: 99%

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

Excler

Rida²,

Priddy

et al. 2011

AIDS Research and Human Retroviruses

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While the long-term goal is to develop highly effective AIDS vaccines, first generation vaccines may be only partially effective. Other HIV prevention modalities such as preexposure prophylaxis with antiretrovirals (PrEP) may have limited efficacy as well. The combined administration of vaccine and PrEP (VAXPREP), however, may have a synergistic effect leading to an overall benefit that is greater than the sum of the individual effects. We propose two test-of-concept trial designs for an AIDS vaccine plus oral or topical ARV. In one design, evidence that PrEP reduces the risk of HIV acquisition is assumed to justify offering it to all participants. A two-arm study comparing PrEP alone to VAXPREP is proposed in which 30 to 60 incident infections are observed to assess the additional benefit of vaccination on risk of infection and setpoint viral load. The demonstrated superiority of VAXPREP does not imply vaccine alone is efficacious. Similarly, the lack of superiority does not imply vaccine alone is ineffective, as antagonism could exist between vaccine and PrEP. In the other design, PrEP is assumed not to be in general use. A 2Â2 factorial design is proposed in which high-risk individuals are randomized to one of four arms: placebo vaccine given with placebo PrEP, placebo vaccine given with PrEP, vaccine given with placebo PrEP, or VAXPREP. Between 60 and 210 infections are required to detect a benefit of vaccination with or without PrEP on risk of HIV acquisition or setpoint viral load, with fewer infections needed when synergy is present.

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Protection of macaques against vaginal SHIV challenge by systemic or mucosal and systemic vaccinations with HIV-envelope

Abstract: The results of this study demonstrate that, in the nonhuman primate model, it is possible for vaccine-elicited immune responses to prevent infection after intravaginal administration of virus.

Cited by 107 publications

References 46 publications

Efficient Generation of Mucosal and Systemic Antigen-Specific CD8⁺T-Cell Responses following Pulmonary DNA Immunization

Efficient Generation of Mucosal and Systemic Antigen-Specific CD8⁺T-Cell Responses following Pulmonary DNA Immunization

Antibody persistence and T-cell balance: Two key factors confronting HIV vaccine development

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

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Protection of macaques against vaginal SHIV challenge by systemic or mucosal and systemic vaccinations with HIV-envelope

Abstract: The results of this study demonstrate that, in the nonhuman primate model, it is possible for vaccine-elicited immune responses to prevent infection after intravaginal administration of virus.

Cited by 107 publications

References 46 publications

Efficient Generation of Mucosal and Systemic Antigen-Specific CD8+T-Cell Responses following Pulmonary DNA Immunization

Efficient Generation of Mucosal and Systemic Antigen-Specific CD8+T-Cell Responses following Pulmonary DNA Immunization

Antibody persistence and T-cell balance: Two key factors confronting HIV vaccine development

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

Contact Info

Product

Resources

About

Efficient Generation of Mucosal and Systemic Antigen-Specific CD8⁺T-Cell Responses following Pulmonary DNA Immunization

Efficient Generation of Mucosal and Systemic Antigen-Specific CD8⁺T-Cell Responses following Pulmonary DNA Immunization