Protection by dendritic cells-based HIV synthetic peptide cocktail vaccine: preclinical studies in the SHIV-rhesus model

Nehete, Pramod N.; Manuri, Pallavi R.; Hill, Lee Forrest; Palmer, J. Lynn; Sastry, K. Jagannadha

doi:10.1016/j.vaccine.2005.01.052

Cited by 26 publications

(27 citation statements)

References 7 publications

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“…These animals had originally been immunized with various formulations of a synthetic peptide vaccine consisting of six conserved epitopes in the envelope (env) protein that have previously been shown to be effective at priming HIV-specific cellular immune responses in multiple animal models and humans [11,40–44]. These six peptides shown aligned to env in Figure 1 generate CD4 and CD8 responses without generating antibody responses.…”

Section: Resultsmentioning

confidence: 99%

“…These six peptides shown aligned to env in Figure 1 generate CD4 and CD8 responses without generating antibody responses. These peptides in various formulations mediate protection in macaques vs. SHIV-KU2 and SHIV-89.6P [43,44]. Prior to the HD-Ad study, macaques Rh51, Rh55, Rh62, and Rh63 had been vaccinated with the six synthetic peptides adjuvanted with FLT-3 ligand, CpG and by loading on dendritic cells (Table 1).…”

Section: Resultsmentioning

confidence: 99%

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Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines

Weaver

Nehete

Buchl

et al. 2009

Viruses

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Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helper-dependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5-immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than in the HD-Ad5 group. In this study, neutralizing antibody and T cell responses were compared between the groups before and after rectal challenge with CCR5-tropic SHIV-SF162P3. When serum samples were assayed for neutralizing antibodies, only weak activity was observed. T cell responses against env epitopes were higher in the serotype-switched group. When these animals were challenged rectally with SHIV-SF162P3, both the Ad5 and serotype-switch groups significantly reduced peak viral loads 2 to 10-fold 2 weeks after infection. Peak viral loads were significantly lower for the serotype-switched group as compared to the HD-Ad5-immunized group. Viral loads declined over 18 weeks after infection with some animals viremia reducing nearly 4 logs from the peak. These data demonstrate significant mucosal vaccine effects after immunization with only env antigens. These data also demonstrate HD-Ad vectors are a robust platform for vaccination.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines

Weaver

Nehete

Buchl

et al. 2009

Viruses

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“…Intradermal injection of autologous antigen-loaded DCs elicited SIV-specific T and B cell responses and, although animals were not protected from infection upon oral challenge, the set point viremia in the vaccinated animals was at least 1 log lower than that seen in non-vaccinated animals (Wagner et al 2002). Similarly, animals immunized with DCs loaded with an envelope peptide cocktail vaccine mounted antigen-specific T cell responses and ultimately reduced plasma viremia following virus challenge with SHIV89.6P (Nehete et al 2005). In an attempt to better target antigens to appropriately activated DCs in order to activate more potent responses, novel strategies involving two types of DC receptors are being explored: receptors mediating antigen uptake (e.g., CD205) and TLRs.…”

Section: 5 Harnessing DC Function To Induce Anti-siv Responsesmentioning

confidence: 99%

Simian Immunodeficiency Virus Interactions with Macaque Dendritic Cells

Teleshova

Derby

Martinelli

et al. 2012

Advances in Experimental Medicine and Biology

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This chapter summarizes advances in the following areas: (1) dendritic cell (DC)-mediated simian immunodeficiency virus (SIV) transmission, (2) role of DCs in innate and adaptive immunity against SIV, and (3) approaches to harness DC function to induce anti-SIV responses. The nonhuman primate (NHP) model of human immunodeficiency virus (HIV) infection in rhesus macaques and other Asian NHP species is highly relevant to advance the understanding of virus–host interactions critical for transmission and disease pathogenesis. HIV infection is associated with changes in frequency, phenotype, and function of the two principal subsets of DCs, myeloid DCs and plasmacytoid DCs. DC biology during pathogenic SIV infection is strikingly similar to that observed in HIV-infected patients. The NHP models provide an opportunity to dissect the requirements for DC-driven SIV infection and to understand how SIV distorts the DC system to its advantage. Furthermore, the SIV model of mucosal transmission enables the study of the earliest events of infection at the portal of entry that cannot be studied in humans, and, importantly, the involvement of DCs. Nonpathogenic infection in African NHP hosts allows investigations into the role of DCs in disease control. Understanding how DCs are altered during SIV infection is critical to the design of therapeutic and preventative strategies against HIV.

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“…A group of six HIV-1 envelope peptides, demonstrated in our previous studies to be effective antigens/immunogens for priming HIV-specific cellular immune responses in multiple animal models and humans, were employed [29][30][31][32][33][34]. The peptides were prepared in the institutional antigen-core facility utilizing FMOC solid phase chemistry on a PTI Symphony Peptide Synthesizer (Protein Technologies Inc., Tucson, AZ) and the purity of the peptides was determined to be >95% by high-pressure liquid chromatography and was validated by mass spectrometry.…”

Section: Peptidesmentioning

confidence: 99%

“…Ad-gag expresses the codon-optimized HIV-1 gag gene. Ad-env-peptide expresses six conserved HIV-1 envelope peptides, 104, 111, 113, 116, 63, and 61 previously shown to elicit MHC I and II-restricted responses in multiple animal models and humans, were employed [29][30][31][32][33][34]. These peptides were expressed as a "string of beads" fusion protein fused to the cterminus of the α-1 antitrypsin secretory leader and a linker to facilitate secretion and MHC II display.…”

Section: Immunization Of Rhesus Macaquesmentioning

confidence: 99%

Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric-coated capsules

Mercier

Nehete

Passeri

et al. 2007

Vaccine

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Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag and a string of six highly-conserved HIV-1 envelope peptides representing broadly cross-reactive CD4 + and CD8 + T cell epitopes. Oral immunization of rhesus macaques with these capsules primed antigen-specific mucosal and systemic immune responses and subsequent intranasal delivery of the envelope peptide cocktail using a mutant cholera toxin adjuvant boosted cellular immune responses including, antigen-specific intracellular IFN-γ-producing CD4 + and CD8 + effector memory T cells in the intestine. These results suggest that the combination of oral adenoviral vector priming followed by intranasal protein/peptide boosting may be an effective mucosal HIV vaccination strategy for targeting viral antigens to the GI tract and priming systemic and mucosal immunity.

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Protection by dendritic cells-based HIV synthetic peptide cocktail vaccine: preclinical studies in the SHIV-rhesus model

Cited by 26 publications

References 7 publications

Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines

Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines

Simian Immunodeficiency Virus Interactions with Macaque Dendritic Cells

Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric-coated capsules

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