Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

Kaur, Amitinder; Sanford, Hannah B.; Garry, Deirdre; Lang, Sabine M.; Klumpp, Sherry A.; Watanabe, Daisuke; Bronson, Roderick T.; Lifson, Jeffrey D.; Rosati, Margherita; Pavlakis, George N.; Felber, Barbara K.; Knipe, David M.; Desrosiers, Ronald C.

doi:10.1016/j.virol.2006.08.007

Cited by 55 publications

(55 citation statements)

References 64 publications

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“…Similar findings were obtained when weeks 6 through 12 were analyzed. The viral loads in the control animals in this study were not significantly different from those in a number of other studies from a number of different laboratories that used the same stock of SIVmac239 (26,30,34,35,65). The two monkeys that were RRV ϩ at the time of vaccination (440-92 and 247-04) fared no worse than the other vaccinated monkeys following SIV challenge.…”

Section: Construction Of Rrv Recombinantscontrasting

confidence: 55%

“…Herpesviruses from different subgroups can be quite distinctly different, targeting different types of cells for primary replication and different types of cells for persistence, and they even carry different compositions of genes. To date, the use of recombinant herpesvirus vectors to express SIV antigens in monkeys has been reported for the alphaherpesvirus herpes simplex virus (HSV) (35,47) and for the betaherpesvirus cytomegalovirus (CMV) (26).…”

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confidence: 99%

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Vaccine Protection against Simian Immunodeficiency Virus in Monkeys Using Recombinant Gamma-2 Herpesvirus

Bilello

Manrique

Shin

et al. 2011

J Virol

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Recombinant strains of replication-competent rhesus monkey rhadinovirus (RRV) were constructed in which strong promoter/enhancer elements were used to drive expression of simian immunodeficiency virus (SIV) Env or Gag or a Rev-Tat-Nef fusion protein. Cultured rhesus monkey fibroblasts infected with each recombinant strain were shown to express the expected protein. Three RRV-negative and two RRV-positive rhesus monkeys were inoculated intravenously with a mixture of these three recombinant RRVs. Expression of SIV Gag was readily detected in lymph node biopsy specimens taken at 3 weeks postimmunization. Impressive anti-SIV cellular immune responses were elicited on the basis of major histocompatibility complex (MHC) tetramer staining and gamma interferon enzyme-linked immunospot (ELISPOT) assays. Responses were much greater in magnitude in the monkeys that were initially RRV negative but were still readily detected in the two monkeys that were naturally infected with RRV at the time of immunization. By 3 weeks postimmunization, responses measured by MHC tetramer staining in the two Mamu-A*01 ؉ RRV-negative monkeys reached 9.3% and 13.1% of all CD8 ؉ T cells in peripheral blood to the Gag CM9 epitope and 2.3% and 7.3% of all CD8 ؉ T cells in peripheral blood to the Tat SL8 epitope. Virus-specific CD8 ؉ T cell responses persisted at high levels up to the time of challenge at 18 weeks postimmunization, and responding cells maintained an effector memory phenotype. Despite the ability of the RRVenv recombinant to express high levels of Env in cultured cells, and despite the appearance of strong anti-RRV antibody responses in immunized monkeys, anti-Env antibody responses were below our ability to detect them. Immunized monkeys, together with three unimmunized controls, were challenged intravenously with 10 monkey infectious doses of SIVmac239. All five immunized monkeys and all three controls became infected with SIV, but peak viral loads were 1.2 to 3.0 log 10 units lower and chronic-phase viral loads were 1.0 to 3.0 log 10 units lower in immunized animals than the geometric mean of unimmunized controls. These differences were statistically significant. Anti-Env antibody responses following challenge indicated an anamnestic response in the vaccinated monkeys. These findings further demonstrate the potential of recombinant herpesviruses as preventive vaccines for AIDS. We hypothesize that this live, replication-competent, persistent herpesvirus vector could match, or come close to matching, live attenuated strains of SIV in the degree of protection if the difficulty with elicitation of anti-Env antibody responses can be overcome.

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Section: Construction Of Rrv Recombinantscontrasting

confidence: 55%

mentioning

confidence: 99%

Vaccine Protection against Simian Immunodeficiency Virus in Monkeys Using Recombinant Gamma-2 Herpesvirus

Bilello

Manrique

Shin

et al. 2011

J Virol

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“…This virus boosts immune responses to DNA vectors in rhesus macaques and results in decreased plasma viral loads after SIV challenge [42]. HSV-1 amplicon vectors have induced potent Gag-specific T cell responses in BALB/c mice, giving further support for the use of HSV-1 as a vector for HIV-1 vaccine delivery [43].…”

Section: Introductionmentioning

confidence: 96%

“…More recently, a replication defective HSV-1 vector with multiple immediate-early gene deletions has been characterized as an SIV vaccine vector [39,42]. This virus boosts immune responses to DNA vectors in rhesus macaques and results in decreased plasma viral loads after SIV challenge [42].…”

Section: Introductionmentioning

confidence: 99%

HIV-189.6 Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in mice

Parker

Rottinghaus

Zajac

et al. 2007

Vaccine

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We have constructed a replication competent, γ 1 34.5-deleted Herpes Simplex Virus type 1 (HSV-1) vector (J200) that expresses the gag gene from Human Immunodeficiency Virus type-1, primary isolate 89.6 (HIV-1 89.6 ), as a candidate vaccine for HIV-1. J200 replicates in vitro, resulting in abundant Gag protein production and accumulation in the extracellular media. Immunization of Balb/ c mice with a single intraperitoneal injection of J200 elicited strong Gag-specific CD8 responses, as measured by intracellular IFN-γ staining and flow cytometry analysis. Responses were highest between 6 weeks and 4 months, but persisted at 9 months post-immunization, the last time-point evaluated. These data highlight the potential utility of neuroattenuated, replication-competent HSV-1 vectors for delivery of HIV-1 immunogens.

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“…One focus is the development and optimization of viral vectors to deliver HIV-1 antigens. Virus-based vaccine vectors under investigation include adenoassociated virus (AAV) [1,2], adenovirus [3][4][5][6][7][8], alphaviruses [9][10][11][12][13], poxviruses [14,15] and herpes simplex virus type 1 (HSV-1) [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

HSV-1 amplicon vectors elicit polyfunctional T cell responses to HIV-1 Env, and strongly boost responses to an adenovirus prime

Duke

Maguire

Keefer

et al. 2007

Vaccine

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HSV-1 amplicon vectors elicit strong T-cell responses to encoded antigens but the qualitative nature of these responses is poorly understood. Antigen-specific CD4 + and CD8 + T-cell responses to amplicon and adenovirus (rAd5) vectors encoding HIV-1 gp120 were assessed following immunization of mice, by performing intracellular cytokine staining for IFNγ, IL-2 and TNFα, following stimulation of splenocytes with a HIV-1 Env peptide pool. The quality of the primary Tcell response to amplicon and rAd5 vectors was strikingly similar, but there were qualitative differences in responses to amplicon vectors that incorporated different promoters upstream of gp120 -suggesting that promoters can significantly influence immune response quality. When prime-boost combinations were studied, a rAd5 prime and amplicon boost elicited the highest T-cell response. Furthermore, protocols that incorporated a rAd5 prime consistently elicited a greater proportion of polyfunctional CD4 + T-cells -regardless of boost. This suggests that initial priming can shape immune response quality after a boost. Overall, these findings provide insight into effective vector combinations for HIV-1 vaccine development.

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Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

Cited by 55 publications

References 64 publications

Vaccine Protection against Simian Immunodeficiency Virus in Monkeys Using Recombinant Gamma-2 Herpesvirus

Vaccine Protection against Simian Immunodeficiency Virus in Monkeys Using Recombinant Gamma-2 Herpesvirus

HIV-189.6 Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in mice

HSV-1 amplicon vectors elicit polyfunctional T cell responses to HIV-1 Env, and strongly boost responses to an adenovirus prime

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