Reduction of viral loads by multigenic DNA priming and adenovirus boosting in the SIVmac-macaque model

Suh, You Suk; Park, Ki S.; Sauermann, Ulrike; Franz, Monika; Norley, Stephen; Wilfingseder, Doris; Stoiber, Heribert; Fagrouch, Zahra; Heeney, Jonathan L.; Hunsmann, Gerhard; Stahl–Hennig∥, Christiane; Sung, Young Chul

doi:10.1016/j.vaccine.2005.10.026

Cited by 34 publications

(27 citation statements)

References 51 publications

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“…Similarly, rhesus macaques that were primed with SIV plasmid DNA, including IL-12 DNA, prior to recombinant vesicular stomatitis virus-SIV administration exhibited the best protective outcome after SHIV 89.6P challenge (13). With regard to a pathogenic SIV challenge model, priming three times with a multigenic SIV plasmid DNA plus IL-12 DNA followed by boosting with a multigenic nonreplicating Ad recombinant without IL-12 led to reduced viral burdens after intrarectal SIV mac251 challenge (60). This study was promising although difficult to evaluate, as few animals were studied and rapid progressors, but not Mamu-A*01 macaques, were eliminated from statistical analysis.…”

Section: Discussionmentioning

confidence: 98%

Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIV_mac251Mucosal Challenge

Demberg

Boyer

Malkevich

et al. 2008

J Virol

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AIDS is one of the greatest pandemics of our time, affecting the health and the social and economic foundations of countries worldwide. A potent human immunodeficiency virus (HIV) vaccine offers the best hope for controlling the spread of the virus. While a single immune correlate has not been identified, both antibodies and CD8 T-cell responses contribute to control of infection with HIV or the related simian immunodeficiency virus (SIV) and disease progression (5, 17, 23, 28, 35-39, 43, 46, 58). Appropriately designed envelope immunogens able to induce broad, potent neutralizing antibodies have not yet been achieved, but vaccine-elicited virus-specific cellular immune responses have been more readily elicited. Both DNA and recombinant viral vectors have emerged as prominent candidate vaccines for this purpose. Although DNA vaccines are not as immunogenic as other vectored vaccines, a variety of approaches can enhance their potency (20). Further, the striking observations that DNA priming followed by boosting with an adenovirus (Ad) or modified vaccinia virus Ankara (MVA)-vectored vaccine elicits enhanced immunity and protective efficacy (3, 59) suggest that among many available vectors (27) other DNA-vector combinations might be equally or more potent.Increasing knowledge of cytokine networks and their influences on the immune system has provided new opportunities for vaccine design and propelled the field toward tailored immune responses. IL-12, first described as natural killer (NK) cell stimulatory factor (25), and IL-15 (18) are among promising candidate cytokine adjuvants for directing such tailored immune responses. Both interleukins have strong effects on NK cells and T cells, influencing the magnitude and quality of cellular responses (1,4,15,30,63). IL-12 acts as adjuvant for both CD4 and CD8 T-cell responses. When administered as a DNA expression vector in combination with other DNA vaccines, it increased cellular immunity in mice (24) and enhanced both humoral and cellular immune responses in rhesus macaques (11,13,57,61). Recently, the addition of IL-12 DNA plasmids to a SIVgag DNA vaccine regimen and to a prime/ boost DNA/vesicular stomatitis virus-SIVgag regimen increased protective efficacy against a SHIV 89.6P challenge (11,13). IL-15, in contrast, primarily increases cellular immunity and is important for development of memory T cells (44).

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Section: Discussionmentioning

confidence: 98%

Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIV_mac251Mucosal Challenge

Demberg

Boyer

Malkevich

et al. 2008

J Virol

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“…An enzyme-linked immunospot (ELISPOT) assay was performed as described previously (10,39), with the modification that cells were stimulated by each of the seven hRSV-F peptide pools at 2 g ml Ϫ1 for each peptide. The positive control consisted of cells stimulated by Staphylococcus enterotoxin B (SEB) at a final concentration 1 g ml Ϫ1 ; negative controls comprised cells kept in medium alone or stimulated by an irrelevant peptide pool derived from human hepatitis C virus sequences (11,12,34).…”

Section: Methodsmentioning

confidence: 99%

Novel Vaccine Regimen Elicits Strong Airway Immune Responses and Control of Respiratory Syncytial Virus in Nonhuman Primates

Grünwald

Tenbusch

Schulte

et al. 2014

J Virol

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Induction of long-lasting immunity against viral respiratory tract infections؉ and CD8 ؉ T cell response in the lower respiratory tract and protection from intranasal hRSV challenge. Thus, parenteral DNA priming followed by booster immunization targeted to a mucosal inductive site constitutes an effective vaccine regimen for eliciting protective immune responses at mucosal effector sites. IMPORTANCEThe human respiratory syncytial virus (hRSV) is the most common cause of severe respiratory tract disease in infancy and leads to substantial morbidity and morality in the elderly. In this study, we compared the immunogenicity and efficacy of several genebased immunization protocols in rhesus macaques. Thereby, we found that the combination of an initially parenterally delivered DNA vaccine with a subsequent atraumatic tonsillar adenoviral vector immunization results in a strong systemic immune response accompanied by an exceptional high T-cell response in the mucosa. Strikingly, these animals were protected against a RSV challenge infection controlling the viral replication indicated by a 1,000-fold-lower viral load in the lower respiratory tract. Since mucosal cellular responses of this strength had not been described in earlier RSV vaccine studies, this heterologous DNA prime-tonsillar boost vaccine strategy is very promising and should be pursued for further preclinical and clinical testing.

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“…Experimental data from most of the animals have been published before. 25,36,50 All monkeys were naive with respect to immunization against SIV or any other antiviral treatment, except for the six immunized monkeys displaying the rapid progressor phenotype. A total of 30 animals were infected with SIV mac 251 grown on monkey peripheral blood mononuclear cells (PBMC).…”

Section: Animals Genealogies and Virusesmentioning

confidence: 99%

“…50 Briefly, purified PBMCs were resuspended in Elispot medium and seeded in triplicate in wells coated with anti-human IFN-g monoclonal antibody. For antigenic stimulation, SIV Gag (15-mer, EVA7066, NIBSC) and Nef peptides (20-mer, EVA777, NIBSC), peptide pools or SEB were included in the medium.…”

Section: Elispot Assaymentioning

confidence: 99%

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

Sauermann

Siddiqui

et al. 2007

Genes Immun

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In both human immunodeficiency virus-infected humans and simian immunodeficiency virus (SIV)-infected macaques, genes encoded in the major histocompatibility complex (MHC) class I region are important determinants of disease progression. However, compared to the human human lymphocyte antigen complex, the macaque MHC region encodes many more class I genes. Macaques with the same immunodominant class I genes express additional Mhc genes with the potential to influence the disease course. We therefore assessed the association between of the Mhc class I haplotypes, rather than single gene variants, and survival time in SIV-infected rhesus macaques (Macaca mulatta). DNA sequence analysis and Mhc genotyping of 245 pedigreed monkeys identified 17 Mhc class I haplotypes that constitute 10 major genotypes. Among 81 vaccination-naive, SIV-infected macaques, 71 monkeys carried at least one Mhc class I haplotype encoding only MHC antigens that were incapable of inducing an effective anti-SIV cytotoxic T lymphocytes response. Study of these macaques enabled us to relate individual Mhc class I haplotypes to slow, medium and rapid disease progression. In a post hoc analysis, classification according to disease progression was found to explain at least 48% of the observed variation of survival time.

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Reduction of viral loads by multigenic DNA priming and adenovirus boosting in the SIVmac-macaque model

Cited by 34 publications

References 51 publications

Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIV_mac251Mucosal Challenge

Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIV_mac251Mucosal Challenge

Novel Vaccine Regimen Elicits Strong Airway Immune Responses and Control of Respiratory Syncytial Virus in Nonhuman Primates

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

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Reduction of viral loads by multigenic DNA priming and adenovirus boosting in the SIVmac-macaque model

Cited by 34 publications

References 51 publications

Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIVmac251Mucosal Challenge

Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIVmac251Mucosal Challenge

Novel Vaccine Regimen Elicits Strong Airway Immune Responses and Control of Respiratory Syncytial Virus in Nonhuman Primates

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

Contact Info

Product

Resources

About

Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIV_mac251Mucosal Challenge

Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIV_mac251Mucosal Challenge