Vaccination with Vaxfectin<sup>®</sup>adjuvanted SIV DNA induces long-lasting humoral immune responses able to reduce SIVmac251 Viremia

Kulkarni, Viraj; Rosati, Margherita; Valentı́n, Antonio; Jalah, Rashmi; Alicea, Candido; Yu, Long-Chuan; Guan, Yongjun; Shen, Xiaoying; Tomaras, Georgia D.; LaBranche, Celia C.; Montefiori, David C.; Irene, Carmela; Prattipati, Rajasekhar; Pinter, Abraham; Sullivan, Sean; Pavlakis, George N.; Felber, Barbara K.

doi:10.4161/hv.25442

Cited by 12 publications

(10 citation statements)

References 61 publications

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“…Naked DNA is picked up poorly by primary cells and its expression is minimal. To improve delivery to the nucleus, several methods have been developed including intramuscular DNA delivery by in vivo electroporation (IM/EP) ([ 55 , 56 , 57 , 58 , 59 , 60 , 61 ] reviewed in [ 62 , 63 , 64 , 65 ]); skin or intradermal electroporation [ 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ], skin patches [ 74 ], liposome delivery with Vaxfectin ® [ 75 , 76 ], DNA formulated in liposomes [ 77 ]; gene gun [ 78 ] or biojector [ 79 , 80 , 81 ]. (iv) Fourth, different strategies to increase the immunogenicity of HIV DNA vaccination in macaques are being pursued, including combination of improved DNA vectors and cytokine DNAs, i.e.…”

Section: Methods To Improve Hiv/siv Dna Vaccine Regimenmentioning

confidence: 99%

HIV DNA Vaccine: Stepwise Improvements Make a Difference

et al. 2014

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Inefficient DNA delivery methods and low expression of plasmid DNA have been major obstacles for the use of plasmid DNA as vaccine for HIV/AIDS. This review describes successful efforts to improve DNA vaccine methodology over the past ~30 years. DNA vaccination, either alone or in combination with other methods, has the potential to be a rapid, safe, and effective vaccine platform against AIDS. Recent clinical trials suggest the feasibility of its translation to the clinic.

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Section: Methods To Improve Hiv/siv Dna Vaccine Regimenmentioning

confidence: 99%

HIV DNA Vaccine: Stepwise Improvements Make a Difference

et al. 2014

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“…Mice vaccinated with DNA encoding HIV Gag plus HSP70 exhibited enhanced T-cell polyfunctionality and proliferation. More conventional approaches, such as use of Vaxfectin, a combination of cationic lipid and neutral lipid formulation, together with plasmid DNA vaccines, have induced potent, sustained Ab responses in NHPs [44]. The number of molecular adjuvant approaches currently being explored for enhancing the immunogenicity of DNA vaccines is a testament to the overall desirability of the DNA vector approach.…”

Section: Dna Vaccinesmentioning

confidence: 99%

New developments in an old strategy: heterologous vector primes and envelope protein boosts in HIV vaccine design

Musich

Robert-Guroff

2016

Expert Review of Vaccines

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Prime/boost vaccination strategies for HIV/SIV vaccine development have been used since the early 1990s and have become an established method for eliciting cell and antibody mediated immunity. Here we focus on induction of protective antibodies, both broadly neutralizing and non-neutralizing, with the viral envelope being the key target antigen. Prime/boost approaches are complicated by the diversity of autologous and heterologous priming vectors, and by various forms of envelope booster immunogens, many still in development as structural studies aim to design stable constructs with exposure of critical epitopes for protective antibody elicitation. This review discusses individual vaccine components, reviews recent prime/boost strategies and their outcomes, and highlights complicating factors arising as greater knowledge concerning induction of adaptive, protective immunity is acquired.

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“…An approach in which rhesus macaques are inoculated intravaginally or intrarectally at regular intervals with a relatively low dose of SIV has been shown to recapitulate the hallmark reduction in viral diversity characteristic of HIV-1 transmission (11)(12)(13)(14). As a result, the repeated, low-dose challenge method has become widely accepted and commonly utilized to model protection against mucosal SIV infection ( [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Despite these numerous studies, the characteristics of the virus that influence intravaginal and intrarectal transmission and protection are incompletely understood.…”

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confidence: 99%

Signatures in Simian Immunodeficiency Virus SIVsmE660 Envelope gp120 Are Associated with Mucosal Transmission but Not Vaccination Breakthrough in Rhesus Macaques

Smith

Kilgore

Kasturi

et al. 2016

J Virol

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Mucosal surfaces are vulnerable to human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection IMPORTANCEMost HIV-1 infections occur across a mucosal barrier, and it is therefore important to understand why these sites are vulnerable and how to protect them with a vaccine. To gain insight into these questions, we studied rhesus macaques that were vaccinated with SIVmac239 and unvaccinated controls to determine whether the SIVsmE660 viral variants that infected these two groups were different. We did not find differences between viral variants in the absence versus presence of vaccination-induced immunity, but we did find that the SIVsmE660 viral variants that infected the monkeys, regardless of vaccination, were different from the dominant population found in the viral challenge inoculum. Our data suggest that the mucosal environments of the vagina and rectum both impose a strong selection for the SIVsmE660 variants in the challenge inoculum that are most like SIV and HIVs that circulate in nature.T he majority of human immunodeficiency virus type 1 (HIV-1) transmission events occur across the genital or rectal mucosa and involve a reduction in the diversity of the infecting viral quasispecies (1). This genetic bottleneck of HIV-1 transmission has been attributed to various features of the HIV-1 envelope (Env) glycoproteins (2-8), resistance to interferon (7, 9), and a selection bias toward consensus residues that confer increased in vivo fitness (10). These studies notwithstanding, it has been difficult to pinpoint the attributes that directly facilitate transmission of a particular HIV-1 variant from a genetically diverse quasispecies. A primary focus of nonhuman primate simian immunodeficiency virus (SIV) challenge models is therefore to recapitulate the critical events that occur during HIV-1 transmission so that any observed effect, including protection, is accurately reflected by the model. An approach in which rhesus macaques are inoculated intravaginally or intrarectally at regular intervals with a relatively low dose of SIV has been shown to recapitulate the hallmark reduction in viral diversity characteristic of HIV-1 transmission (11)(12)(13)(14). As a result, the repeated, low-dose challenge method has become widely accepted and commonly utilized to model protection against mucosal SIV infection (14-32). Despite these numerous studies, the characteristics of the virus that influence intravaginal and intrarectal transmission and protection are incompletely understood.We previously demonstrated that an SIVmac239-based regimen consisting of two DNA primes followed by two modified vaccinia virus Ankara (MVA) boosts provided significant protection against repeated, low-dose SIVsmE660 intrarectal challenge. Including granulocyte-macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) as an adjuvant with the DNA Citation Smith SA, Kilgore KM, Kasturi SP, Pulendran B, Hunter E, Amara RR, Derdeyn CA. 2016. Signatures in simian immunodeficiency virus SIVsmE660 envelop...

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Vaccination with Vaxfectin^®adjuvanted SIV DNA induces long-lasting humoral immune responses able to reduce SIVmac251 Viremia

Cited by 12 publications

References 61 publications

HIV DNA Vaccine: Stepwise Improvements Make a Difference

HIV DNA Vaccine: Stepwise Improvements Make a Difference

New developments in an old strategy: heterologous vector primes and envelope protein boosts in HIV vaccine design

Signatures in Simian Immunodeficiency Virus SIVsmE660 Envelope gp120 Are Associated with Mucosal Transmission but Not Vaccination Breakthrough in Rhesus Macaques

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Vaccination with Vaxfectin®adjuvanted SIV DNA induces long-lasting humoral immune responses able to reduce SIVmac251 Viremia

Cited by 12 publications

References 61 publications

HIV DNA Vaccine: Stepwise Improvements Make a Difference

HIV DNA Vaccine: Stepwise Improvements Make a Difference

New developments in an old strategy: heterologous vector primes and envelope protein boosts in HIV vaccine design

Signatures in Simian Immunodeficiency Virus SIVsmE660 Envelope gp120 Are Associated with Mucosal Transmission but Not Vaccination Breakthrough in Rhesus Macaques

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Vaccination with Vaxfectin^®adjuvanted SIV DNA induces long-lasting humoral immune responses able to reduce SIVmac251 Viremia