Oral
            <i>Salmonella typhimurium</i>
            Vaccine Expressing Circumsporozoite Protein Protects Against Malaria

Sadoff, J. C.; Wr, Ballou; Baron, L. S.; Majarian, W R; Brey, RN; Wt, Hockmeyer; Young, JF; Cryz, S J; Ou, Jonathan T.; Lowell, GH

doi:10.1126/science.3281260

Cited by 240 publications

(97 citation statements)

References 23 publications

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“…The CS proteins of all malaria species contain a central segment of species-specific amino acid repeat sequences flanked by non-repeat regions [8,9]. In the case of P. falciparum, the central portion contains approximately 40 repeats of the amino acid sequence asparagin-alanine-asparagines-proline (NANP) and several asparagines-valine-aspartic acid-proline (NVDP) repeats [10].…”

Section: Initial Circumsporozoite Protein Vaccinesmentioning

confidence: 99%

Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research

Heppner

Kester

Ockenhouse

et al. 2005

Vaccine

179

101

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The goal of the Malaria Vaccine Program at the Walter Reed Army Institute of Research (WRAIR) is to develop a licensed multi-antigen, multi-stage vaccine against Plasmodium falciparum able to prevent all symptomatic manifestations of malaria by preventing parasitemia. A secondary goal is to limit disease in vaccinees that do develop malaria. Malaria prevention will be achieved by inducing humoral and cellular immunity against the pre-erythrocytic circumsporozoite protein (CSP) and the liver stage antigen-1 (LSA-1). The strategy to limit disease will target immune responses against one or more blood stage antigens, merozoite surface protein-1 (MSP-1) and apical merozoite antigen-1 (AMA-1). The induction of T-and B-cell memory to achieve a sustained vaccine response may additionally require immunization with an adenovirus vector such as adenovirus serotype 35. RTS,S, a CSP-derived antigen developed by GlaxoSmithKline Biologicals in collaboration with the Walter Reed Army Institute of Research over the past 17 years, is the cornerstone of our program. RTS,S formulated in AS02A (a GSK proprietary formulation) is the only vaccine candidate shown in field trials to prevent malaria and, in one instance, to limit disease severity. Our vaccine development plan requires proof of an individual antigen's efficacy in a Phase 2 laboratory challenge or field trial prior to its integration into an RTS,S-based, multi-antigen vaccine. Progress has been accelerated through extensive partnerships with industrial, D.G. Heppner Jr. et al. / Vaccine 23 (2005) [2243][2244][2245][2246][2247][2248][2249][2250] academic, governmental, and non-governmental organizations. Recent safety, immunogenicity, and efficacy trials in the US and Africa are presented, as well as plans for the development of a multi-antigen vaccine.

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Section: Initial Circumsporozoite Protein Vaccinesmentioning

confidence: 99%

Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research

Heppner

Kester

Ockenhouse

et al. 2005

Vaccine

179

101

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“…The mice developed a genetically restricted, antigen-specific, CD8+ T-cell-dependent immune response that protected some of the mice against malaria. This protection was antibody independent (1,86).…”

Section: Transmission-blocking and Pathogenicity Antigensmentioning

confidence: 98%

Malaria vaccine development

Jones

Hoffman

1994

Clin Microbiol Rev

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The malaria parasite life cycle presents several targets for attack, but these different parts of the life cycle are susceptible to different types of host immune response. For example, the sporozoite is most sensitive to immune antibody, while liver stage parasites can be eliminated by cytotoxic T lymphocytes. Attachment of merozoites to erythrocytes, on the other hand, can be blocked by antibody. Convincing experimental evidence shows that completely protective immunity to malaria can be induced. The challenge now is to design recombinant or synthetic vaccines that induce the right types of immune responses to specific life cycle stages. This requires the identification and characterization of B- and T-lymphocyte epitopes expressed by the parasite or by parasitized host cells. These epitopes must be incorporated into a delivery system that maximizes the interaction between the vaccine epitopes and the host immune system. Many epitopes from several parts of the life cycle are already characterized; development of multivalent vaccines, that is, vaccines which contain immunogens from more than one part of the life cycle, is a promising area for research efforts.

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“…Initial studies using an attenuated strain of Salmonella typhimurium transformed with plasmid expressing the CS gene of P. berghei and P. yoelii demonstrated the capacity of this vector to induce CD8 + T cell dependent immune protection in 55%-70% of immunized BALB/c mice (Sadoff et al 1988, Aggarwall et al1990, Flyn et al 1990). This approach was recently evaluated in humans immunized orally with recombinant S. typhi expressing the CS protein of P. falciparum.…”

Section: Induction Of Anti-malaria Cd8 + T Cells Using Live Recombinamentioning

confidence: 99%

Protective CD8+ T cell responses against the pre-erythrocytic stages of malaria parasites: an overview

Oliveira-Ferreira¹,

Daniel-Ribeiro²

2001

Mem. Inst. Oswaldo Cruz

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Oral Salmonella typhimurium Vaccine Expressing Circumsporozoite Protein Protects Against Malaria

Cited by 240 publications

References 23 publications

Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research

Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research

Malaria vaccine development

Protective CD8+ T cell responses against the pre-erythrocytic stages of malaria parasites: an overview

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