Immune responses against a liver-stage malaria antigen induced by simian adenoviral vector AdCh63 and MVA prime–boost immunisation in non-human primates

Capone, Stefania; Reyes-Sandoval, Arturo; Naddeo, Mariarosaria; Siani, Loredana; Ammendola, Virginia; Rollier, Christine S.; Nicosia, Alfredo; Colloca, Stefano; Cortese, Riccardo; Folgori, Antonella; Hill, Adrian V. S.

doi:10.1016/j.vaccine.2010.10.041

Cited by 68 publications

(69 citation statements)

References 31 publications

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“…Importantly, the high level of immunogenicity of the top ranking ChAd3 and PanAd3 was confirmed in non-human primates, where they induced a level of T-cell response comparable to that of Ad5 even at low dose (10 8 vp). Similarly, we recently showed that another high scoring ChAd vector (ChAd63) encoding for the Malaria TRAP antigen induced a very potent T-cell response in Rhesus macaques (35). Notably, the ability of ChAds to induce strong cellular immunity is not an antigen-dependent phenomenon as we could induce substantial T-cell response by immunising rodents and non human primates with ChAd vectors encoding different antigens from infectious agents such as HIV, HCV, Malaria, HSV2, Ebola, RSV and Influenza as well as cancer.…”

Section: Discussionmentioning

confidence: 77%

Vaccine Vectors Derived from a Large Collection of Simian Adenoviruses Induce Potent Cellular Immunity Across Multiple Species

Colloca¹,

Barnes

Folgori³

et al. 2012

Sci. Transl. Med.

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262

308

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Replication defective Adenovirus vectors based on the human serotype 5 (Ad5) have been shown to induce protective immune responses against diverse pathogens and cancer in animal models and to elicit robust and sustained cellular immunity in humans. However, most humans have anti-Ad5 neutralising antibodies that can impair the immunological potency of such vaccines. Here we show that most other human Adenoviruses from rare serotypes are far less potent as vaccine vectors than Ad5 in mice and non-human primates, casting doubt on their potential efficacy in humans. To identify novel vaccine carriers suitable for vaccine delivery in humans we isolated and sequenced over a thousand Adenovirus strains from chimpanzees (ChAd). Replication-defective vectors were generated from different ChAd serotypes and were screened for neutralization by human sera and for ability to grow in human cell lines already approved for clinical studies. Most importantly, we devised a screening strategy to rank the ChAd vectors by immunological potency in mice which predicts their immunogenicity in non-human primates and humans. The vectors studied varied by up to a thousand-fold in potency for CD8 T cell induction in mice. Two of the Europe PMC Funders Group

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Section: Discussionmentioning

confidence: 77%

Vaccine Vectors Derived from a Large Collection of Simian Adenoviruses Induce Potent Cellular Immunity Across Multiple Species

Colloca¹,

Barnes

Folgori³

et al. 2012

Sci. Transl. Med.

Self Cite

262

308

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“…Specifically, the ability of prime-boost immunization with heterologous vectors to elicit robust cellular and humoral immune responses has been well documented (7,18,23). In this study, we first evaluated the potential of different prime-boost combinations involving replication-defective lymphocytic choriomeningitis virus (rLCMV), a genebased viral vector that elicits potent CD8 immune responses (17).…”

mentioning

confidence: 99%

Gene-Based Vaccination with a Mismatched Envelope Protects against Simian Immunodeficiency Virus Infection in Nonhuman Primates

Flatz

Cheng

Wang

et al. 2012

J Virol

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The RV144 trial demonstrated that an experimental AIDS vaccine can prevent human immunodeficiency virus type 1 (HIV-1) infection in humans. Because of its limited efficacy, further understanding of the mechanisms of preventive AIDS vaccines remains a priority, and nonhuman primate (NHP) models of lentiviral infection provide an opportunity to define immunogens, vectors, and correlates of immunity. In this study, we show that prime-boost vaccination with a mismatched SIV envelope (Env) gene, derived from simian immunodeficiency virus SIVmac239, prevents infection by SIVsmE660 intrarectally. Analysis of different gene-based prime-boost immunization regimens revealed that recombinant adenovirus type 5 (rAd5) prime followed by replication-defective lymphocytic choriomeningitis virus (rLCMV) boost elicited robust CD4 and CD8 T-cell and humoral immune responses. This vaccine protected against infection after repetitive mucosal challenge with efficacies of 82% per exposure and 62% cumulatively. No effect was seen on viremia in infected vaccinated monkeys compared to controls. Protection correlated with the presence of neutralizing antibodies to the challenge viruses tested in peripheral blood mononuclear cells. These data indicate that a vaccine expressing a mismatched Env gene alone can prevent SIV infection in NHPs and identifies an immune correlate that may guide immunogen selection and immune monitoring for clinical efficacy trials.

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“…The resulting plasmids were inserted into the E1 locus of pAd/PL-DEST (Invitrogen) by in vitro recombination using LR clonase (Invitrogen). Expression cassettes were inserted into the E1 locus of a genomic clone of ChAd63 using homologous recombination in BJ5183 E. coli as previously described [55].…”

Section: Methodsmentioning

confidence: 99%

4-1BBL Enhances CD8+ T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques

et al. 2014

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T cells play a central role in the immune response to many of the world’s major infectious diseases. In this study we investigated the tumour necrosis factor receptor superfamily costimulatory molecule, 4-1BBL (CD137L, TNFSF9), for its ability to increase T cell immunogenicity induced by a variety of recombinant vectored vaccines. To efficiently test this hypothesis, we assessed a number of promoters and developed a stable bi-cistronic vector expressing both the antigen and adjuvant. Co-expression of 4-1BBL, together with our model antigen TIP, was shown to increase the frequency of murine antigen-specific IFN-γ secreting CD8+ T cells in three vector platforms examined. Enhancement of the response was not limited by co-expression with the antigen, as an increase in CD8+ immunogenicity was also observed by co-administration of two vectors each expressing only the antigen or adjuvant. However, when this regimen was tested in non-human primates using a clinical malaria vaccine candidate, no adjuvant effect of 4-1BBL was observed limiting its potential use as a single adjuvant for translation into a clinical vaccine.

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Immune responses against a liver-stage malaria antigen induced by simian adenoviral vector AdCh63 and MVA prime–boost immunisation in non-human primates

Cited by 68 publications

References 31 publications

Vaccine Vectors Derived from a Large Collection of Simian Adenoviruses Induce Potent Cellular Immunity Across Multiple Species

Vaccine Vectors Derived from a Large Collection of Simian Adenoviruses Induce Potent Cellular Immunity Across Multiple Species

Gene-Based Vaccination with a Mismatched Envelope Protects against Simian Immunodeficiency Virus Infection in Nonhuman Primates

4-1BBL Enhances CD8+ T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques

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