Improved T cell responses to Plasmodium falciparum circumsporozoite protein in mice and monkeys induced by a novel formulation of RTS,S vaccine antigen

Mettens, Pascal; Dubois, Patrice; Demoitié, Marie-Ange; Bayat, Babak; Donner, Marie-Noëlle; Bourguignon, Patricia; Stewart, V. Ann; Heppner, D. Gray; Garçon, Nathalie; Cohen, Joe

doi:10.1016/j.vaccine.2007.12.018

Cited by 74 publications

(64 citation statements)

References 66 publications

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“…60,61 Furthermore, the RTS,S/AS01 candidate induced CS specific cell mediated immune responses of a predominantly Th1 type that was significantly greater than that induced by RTS,S/AS02. 62 The superior Adjuvant System activity of RTS,S/AS01 B compared to RTS,S/ AS02 A observed in the rhesus monkey model was subsequently confirmed in malaria-naïve adults in a Phase 2a challenge study conducted at WRAIR. Greater anti-CS antibody responses and superior CS-specific multifunctional CD4…”

Section: From Early Cs-based Vaccines To Rtssmentioning

confidence: 88%

From the circumsporozoite protein to the RTS,S/AS candidate vaccine

Cohen

Nussenzweig²,

Nussenzweig³

et al. 2010

Human Vaccines

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Section: From Early Cs-based Vaccines To Rtssmentioning

confidence: 88%

From the circumsporozoite protein to the RTS,S/AS candidate vaccine

Cohen

Nussenzweig²,

Nussenzweig³

et al. 2010

Human Vaccines

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224

173

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“…In conclusion, we show that a full-length P. falciparum CS protein when combined with poly(I·C)LC or GLA-SE induces potent immunity and protection in mice. Moreover, poly(I·C)LC is an effective adjuvant for eliciting such responses in NHPs, providing a predictive model for what might occur in humans (20,21,70,71). It is possible that the increased breadth of CSP responses with a full-length CSP (compared to the CSP responses with truncated RTS,S) and/or the enhanced CD4 ϩ Th1 immunity that would potentially be elicited by poly(I·C)LC would enhance protection and/or durability.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, studies using irradiated sporozoites for vaccination have shown a critical requirement for gamma interferon (IFN-␥) and cellular immunity in mediating protection against malaria (18,19). Accordingly, optimizing CD4 ϩ T cell-derived IFN-␥ production after RTS,S vaccination by altering the adjuvant formulation enhanced protection (20)(21)(22). Using the Toll-like receptor 4 (TLR4) ligand MPL and saponin (QS-21) in an oil-water emulsion (AS02) or liposome (AS01B or -E) formulation led to a strong antibody response and increased CD4 ϩ T cell immunity compared to levels induced with older formulations with alum and MPL (21,23,24).…”

mentioning

confidence: 99%

“…Accordingly, optimizing CD4 ϩ T cell-derived IFN-␥ production after RTS,S vaccination by altering the adjuvant formulation enhanced protection (20)(21)(22). Using the Toll-like receptor 4 (TLR4) ligand MPL and saponin (QS-21) in an oil-water emulsion (AS02) or liposome (AS01B or -E) formulation led to a strong antibody response and increased CD4 ϩ T cell immunity compared to levels induced with older formulations with alum and MPL (21,23,24). Collectively, these data highlight the importance of adjuvant formulations in optimizing immunity and protection.…”

mentioning

confidence: 99%

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Full-Length Plasmodium falciparum Circumsporozoite Protein Administered with Long-Chain Poly(I·C) or the Toll-Like Receptor 4 Agonist Glucopyranosyl Lipid Adjuvant-Stable Emulsion Elicits Potent Antibody and CD4⁺T Cell Immunity and Protection in Mice

et al. 2013

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؉ T cell responses. Finally, protective immunity was also induced using the Toll-like receptor 4 agonist glucopyranosyl lipid adjuvantstable emulsion (GLA-SE) as the adjuvant, which also correlated with high antibody titers yet CD4 ؉ T cell immunity that was significantly less potent than that with poly(I·C)LC. Overall, these data suggest that full-length CS proteins and poly(I·C)LC or GLA-SE offer a simple vaccine formulation to be used alone or in combination with other vaccines for preventing malaria infection. Malaria infection with Plasmodium falciparum causes more than 600,000 deaths annually as well as significant morbidity worldwide (1). A range of efforts to control and treat malaria include public health measures such as insecticide-treated bed nets, indoor residual spraying, and widespread usage of antimalarial drugs. Despite the impact of these approaches, the most cost-effective solution to prevent infection and to ultimately control the malaria endemic is to develop a vaccine.Currently, the most advanced vaccine tested in humans against P. falciparum infection is RTS,S, which targets the circumsporozoite (CS) protein (CSP), the major and most abundant antigen expressed on the surfaces of infectious sporozoites. RTS,S given with the AS01 adjuvant (RTS,S/AS01) shows ϳ30% protection against clinical disease and severe malaria (2, 3). Thus, while these first results in phase III trials with RTS,S/AS01 are encouraging, there may be additional approaches for further optimizing the breadth, potency, and duration of immunity against the CSP using different immunogens or more-potent adjuvants. In terms of antigen design, RTS,S is comprised of a truncated form of CSP containing the central repeat region, NANP, which is a target for antibody-mediated neutralization, as well as CD8 ϩ and CD4 ϩ T cell epitopes at the C-terminal end. This truncated CS protein is then fused to the hepatitis B virus surface antigen, creating an immunogenic particle. Therefore, using a more-full-length CSP, including the N-terminal end and the R1 region of CSP as well as the minor repeat region (NVDP), might favor broader antibody responses than against the NANP repeat region alone (4-8). Moreover, a full-length CSP may provide additional T cell epitopes, leading to increased breadth of cellular immunity, which could also enhance protection. Another approach is to enhance the humoral and cellular immune responses by altering the type of adjuvant given with the full-length-CSP-based protein vaccine.Early studies in mice showed that protection was associated with high antibody titers (9-11). The next generation of malaria vaccines combined CSP with more-potent adjuvants, like Pseu-

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“…AS04 is used for vaccines against human hepatitis B virus (5) and human papillomavirus (21). AS01 and AS02 are currently under development as adjuvants for antimalaria vaccines (17).…”

mentioning

confidence: 99%

Modulation of Gene Expression Related to Toll-Like Receptor Signaling in Dendritic Cells by Poly(γ-Glutamic Acid) Nanoparticles

Hamasaki

Uto

Akagi

et al. 2010

Clin Vaccine Immunol

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Improved T cell responses to Plasmodium falciparum circumsporozoite protein in mice and monkeys induced by a novel formulation of RTS,S vaccine antigen

Cited by 74 publications

References 66 publications

From the circumsporozoite protein to the RTS,S/AS candidate vaccine

From the circumsporozoite protein to the RTS,S/AS candidate vaccine

Full-Length Plasmodium falciparum Circumsporozoite Protein Administered with Long-Chain Poly(I·C) or the Toll-Like Receptor 4 Agonist Glucopyranosyl Lipid Adjuvant-Stable Emulsion Elicits Potent Antibody and CD4⁺T Cell Immunity and Protection in Mice

Modulation of Gene Expression Related to Toll-Like Receptor Signaling in Dendritic Cells by Poly(γ-Glutamic Acid) Nanoparticles

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Improved T cell responses to Plasmodium falciparum circumsporozoite protein in mice and monkeys induced by a novel formulation of RTS,S vaccine antigen

Cited by 74 publications

References 66 publications

From the circumsporozoite protein to the RTS,S/AS candidate vaccine

From the circumsporozoite protein to the RTS,S/AS candidate vaccine

Full-Length Plasmodium falciparum Circumsporozoite Protein Administered with Long-Chain Poly(I·C) or the Toll-Like Receptor 4 Agonist Glucopyranosyl Lipid Adjuvant-Stable Emulsion Elicits Potent Antibody and CD4+T Cell Immunity and Protection in Mice

Modulation of Gene Expression Related to Toll-Like Receptor Signaling in Dendritic Cells by Poly(γ-Glutamic Acid) Nanoparticles

Contact Info

Product

Resources

About

Full-Length Plasmodium falciparum Circumsporozoite Protein Administered with Long-Chain Poly(I·C) or the Toll-Like Receptor 4 Agonist Glucopyranosyl Lipid Adjuvant-Stable Emulsion Elicits Potent Antibody and CD4⁺T Cell Immunity and Protection in Mice