Impact of Recombinant Adenovirus Serotype 35 Priming versus Boosting of a<i>Plasmodium falciparum</i>Protein: Characterization of T- and B-Cell Responses to Liver-Stage Antigen 1

Rodriguez, Ariane; Goudsmit, Jaap; Companjen, Arjen; Mintardjo, Ratna; Gillissen, Gert; Tax, Dennis; Sijtsma, Jeroen; Weverling, Gerrit Jan; Holterman, Lennart; Lanar, David E.; Havenga, Menzo; Radošević, Katarina

doi:10.1128/iai.01614-07

Cited by 21 publications

(17 citation statements)

References 60 publications

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“…Importantly, while the overall CS-specific IgG levels were not affected relative to the responses induced with an entirely CS protein-based vaccination regimen, the CS protein/Ad35.CS regimen elicited a more Th1-type response. These results corroborated our earlier findings in which primeboost regimens comprised of Ad35 vaccine vectors expressing CS or LSA-1 and RTS,S or a LSA-1 protein vaccine resulted in potent Th1-type T-cell responses and high-level humoral responses (45,52).…”

Section: Discussionsupporting

confidence: 81%

“…CS-specific T-cell assays. CS-specific cellular immune responses in vaccinated mice were assessed using an IFN-␥ ELISPOT assay, intracellular cytokine staining in combination with surface staining of CD4 and CD8 markers (ICS) as described previously elsewhere (4,45), and a cytometric bead array (CBA) assay.…”

Section: Characterization Of the Yeast-produced Cs Proteinmentioning

confidence: 99%

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The Th1 Immune Response toPlasmodium falciparumCircumsporozoite Protein Is Boosted by Adenovirus Vectors 35 and 26 with a Homologous Insert

Radošević

Rodriguez

Lemckert

et al. 2010

Clin Vaccine Immunol

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The most advanced malaria vaccine, RTS,S, is comprised of an adjuvant portion of the Plasmodium falciparum circumsporozoite (CS) protein fused to and admixed with the hepatitis B virus surface antigen. This vaccine confers short-term protection against malaria infection, with an efficacy of about 50%, and induces particularly B-cell and CD4؉ T-cell responses. In the present study, we tested by the hypothesis that the Th1 immune response to CS protein, in particular the CD8 ؉ T-cell response, which is needed for strong and lasting malaria immunity, is boosted to sustainable levels vectors adenovirus and 26 with an homologous insert 35 (Ad35.CS/Ad26.CS). In this study, we evaluated immune responses induced with vaccination regimens based on an adjuvant-containing, yeast-produced complete CS protein followed by two recombinant low-seroprevalence adenoviruses expressing P. falciparum CS antigen, Ad35.CS (subgroup B) and Ad26.CS (subgroup D). Our results show that (i) the yeast (Hansenula polymorpha)produced, adjuvanted full-length CS protein is highly potent in inducing high CS-specific humoral responses in mice but produces poor T-cell responses, (ii) the Ad35.CS vector boosts the gamma interferon-positive (IFN-␥

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Section: Discussionsupporting

confidence: 81%

Section: Characterization Of the Yeast-produced Cs Proteinmentioning

confidence: 99%

The Th1 Immune Response toPlasmodium falciparumCircumsporozoite Protein Is Boosted by Adenovirus Vectors 35 and 26 with a Homologous Insert

Radošević

Rodriguez

Lemckert

et al. 2010

Clin Vaccine Immunol

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“…To avoid the potential deleterious effect of the induction of anti-vector immunity by immunization, we tested several immunization regimens that involved a single Ad vector immunization. The optimized immunization regimen we describe here are in agreement with previous reports that highlighted the relevance of Ad vectors as a robust priming agent in heterologous immunization regimens that involve recombinant proteins (22, 38). …”

Section: Discussionsupporting

confidence: 90%

A Recombinant Chimeric Ad5/3 Vector Expressing a Multistage Plasmodium Antigen Induces Protective Immunity in Mice Using Heterologous Prime-Boost Immunization Regimens

Cabrera-Mora

Fonseca

Singh

et al. 2016

The Journal of Immunology

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An ideal malaria vaccine should target several stages of the parasite life cycle and induce anti-parasite and anti-disease immunity. We have reported a Plasmodium yoelii chimeric multi-stage recombinant protein (PyLPC/RMC), engineered to express several autologous T cell epitopes and sequences derived from the circumsporozoite protein (CSP) and the merozoite surface protein 1 (MSP-1). This chimeric protein elicits protective immunity, mediated by CD4+ T cells and neutralizing antibodies. However, experimental evidence from pre-erythrocytic vaccine candidates and irradiated sporozoites has shown that CD8+ T cells play a significant role in protection. Recombinant viral vectors have been used as a vaccine platform to elicit effective CD8+ T cell responses. The human adenovirus serotype 5 (Ad5) has been tested in malaria vaccine clinical trials with excellent safety profile. Nevertheless, a major concern for the use of Ad5 is the high prevalence of anti-vector neutralizing antibodies in humans, hampering its immunogenicity. To minimize the impact of anti-vector pre-existing immunity we developed a chimeric Ad5/3 vector in which the knob region of Ad5 was replaced with that of Ad3, conferring partial resistance to anti-Ad5 neutralizing antibodies. Furthermore, we implemented heterologous adenovirus/protein immunization regimens which include a single immunization with recombinant Ad vectors. Our data show that immunization with the recombinant Ad5/3 vector induces protective efficacy indistinguishable from that elicited by Ad5. Our study also demonstrate that the dose of the Ad vectors has an impact on the memory profile and protective efficacy. The results support further studies with Ad5/3 for malaria vaccine development.

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“…In addition, Ad35 is a promising vector for clinical gene transfer and vaccination, in part due to the low seroprevalence of neutralizing antibodies in the population (100). For example, an Ad35-based malaria vaccine was shown to protect mice from Plasmodium falciparum sporozoites (77) and induced potent T-cell immunity (83). In addition, Ad35 vectors injected into tissues of nonhuman primates gave rise to specific gene expression at sites of injection in most organs, indicating the high versatility of Ad35 (86,87).…”

mentioning

confidence: 99%

Macropinocytotic Uptake and Infection of Human Epithelial Cells with Species B2 Adenovirus Type 35

Kälin

Amstutz

Gastaldelli

et al. 2010

J Virol

103

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Human adenovirus serotype 35 (HAdV-35; here referred to as Ad35) causes kidney and urinary tract infections and infects respiratory organs of immunocompromised individuals. Unlike other adenoviruses, Ad35 has a low seroprevalence, which makes Ad35-based vectors promising candidates for gene therapy. Ad35 utilizes CD46 and integrins as receptors for infection of epithelial and hematopoietic cells. Here we show that infectious entry of Ad35 into HeLa cells, human kidney HK-2 cells, and normal human lung fibroblasts strongly depended on CD46 and integrins but not heparan sulfate and variably required the large GTPase dynamin. Ad35 infections were independent of expression of the carboxy-terminal domain of AP180, which effectively blocks clathrin-mediated uptake. Ad35 infections were inhibited by small chemicals against serine/ threonine kinase Pak1 (p21-activated kinase), protein kinase C (PKC), sodium-proton exchangers, actin, and acidic organelles. Remarkably, the F-actin inhibitor jasplakinolide, the Pak1 inhibitor IPA-3, or the sodiumproton exchange inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA) blocked endocytic uptake of Ad35. Dominant-negative proteins or small interfering RNAs against factors driving macropinocytosis, including the small GTPase Rac1, Pak1, or the Pak1 effector C-terminal binding protein 1 (CtBP1), potently inhibited Ad35 infection. Confocal laser scanning microscopy, electron microscopy, and live cell imaging showed that Ad35 colocalized with fluid-phase markers in large endocytic structures that were positive for CD46, ␣ integrins, and also CtBP1. Our results extend earlier observations with HAdV-3 (Ad3) and establish macropinocytosis as an infectious pathway for species B human adenoviruses in epithelial and hematopoietic cells.

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Impact of Recombinant Adenovirus Serotype 35 Priming versus Boosting of aPlasmodium falciparumProtein: Characterization of T- and B-Cell Responses to Liver-Stage Antigen 1

Cited by 21 publications

References 60 publications

The Th1 Immune Response toPlasmodium falciparumCircumsporozoite Protein Is Boosted by Adenovirus Vectors 35 and 26 with a Homologous Insert

The Th1 Immune Response toPlasmodium falciparumCircumsporozoite Protein Is Boosted by Adenovirus Vectors 35 and 26 with a Homologous Insert

A Recombinant Chimeric Ad5/3 Vector Expressing a Multistage Plasmodium Antigen Induces Protective Immunity in Mice Using Heterologous Prime-Boost Immunization Regimens

Macropinocytotic Uptake and Infection of Human Epithelial Cells with Species B2 Adenovirus Type 35

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