Evaluation of the safety and immunogenicity of Plasmodium falciparum apical membrane antigen 1, merozoite surface protein 1 or RTS,S vaccines with adjuvant system AS02A administered alone or concurrently in rhesus monkeys

Pichyangkul, Sathit; Tongtawe, Pongsri; Kum-Arb, Utaiwan; Yongvanitchit, Kosol; Gettayacamin, Montip; Hollingdale, Michael R.; Limsalakpetch, Amporn; Stewart, V. Ann; Lanar, D.; Dutta, Sandeep; Angov, Evelina; Ware, Lisa A.; Bergmann‐Leitner, Elke S.; House, Brent; Voss, Gérald; Dubois, Marie-Claude; Cohen, Joe; Fukuda, Mark M.; Heppner, D. Gray; Miller, R. Scott

doi:10.1016/j.vaccine.2009.10.022

Cited by 33 publications

(30 citation statements)

References 61 publications

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“…This finding was confirmed by sporozoite challenge in which no significant differences were observed in survival between mice immunized against PyMSP1 42 alone, compared with mice immunized against both PyMSP1 42 and PyCSP. These results are in agreement with a study combining the RTS,S (CSP vaccine) with MSP1 42 and AMA1 protein vaccines in rhesus macaques (15), in which there was no interference between Ab responses against RTS,S and MSP1 42 . However the authors reported that MSP1 42 immunization interfered with both AMA1-specific Abs and IFN-g production, and it will be important in future studies to ascertain whether antigenic interference is an Ag-specific phenomenon or related to specific vaccine delivery platforms.…”

Section: Discussionsupporting

confidence: 91%

“…It is suggested that a secondgeneration vaccine will need to provide .80% efficacy for at least 4 y to justify deployment (14). One possible strategy that has been investigated preclinically in rhesus macaques is the combination of RTS,S/AS02 A with protein-in-adjuvant vaccine candidates for the blood-stage Ags MSP1 and AMA1 (15). This study found that AMA1-specific Ab responses are reduced when AMA1 is coadministered with either RTS,S or the 42-kDa C terminus of MSP1 (MSP1 42 ).…”

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confidence: 92%

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Combining Liver- and Blood-Stage Malaria Viral-Vectored Vaccines: Investigating Mechanisms of CD8+ T Cell Interference

Forbes

Biswas

Collins

et al. 2011

The Journal of Immunology

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Replication-deficient adenovirus and modified vaccinia virus Ankara (MVA) vectors expressing single pre-erythrocytic or blood-stage Plasmodium falciparum antigens have entered clinical testing using a heterologous prime-boost immunization approach. Here we investigated the utility of the same immunization regime when combining viral vectored vaccines expressing the 42kDa C-terminus of the blood-stage antigen merozoite surface protein 1 (MSP142) and the pre-erythrocytic antigen circumsporozoite protein (CSP) in the P. yoelii mouse model. We find that vaccine co-administration leads to maintained antibody responses and efficacy against blood-stage infection, but reduced secondary CD8+ T cell responses against both antigens and efficacy against liver-stage infection. CD8+ T cell interference can be minimized by co-administering the MVA vaccines at separate sites, resulting in enhanced liver-stage efficacy in mice immunized against both antigens compared to just one. CD8+ T cell interference (following MVA co-administration as a mixture) may partly be caused by a lack of physiological space for high magnitude responses against multiple antigens, but is not caused by competition for presentation of antigen on MHC class I molecules, nor is it due to restricted T cell access to APCs presenting both antigens. Instead, enhanced killing of peptide-pulsed cells is observed in mice possessing pre-existing T cells against two antigens, in comparison to just one, suggesting priming against multiple antigens may in part reduce the potency of multi-antigen MVA vectors to stimulate secondary CD8+ T cell responses. These data have important implications for the development of a multi-stage or multi-component viral vectored malaria vaccine for use in humans.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 92%

Combining Liver- and Blood-Stage Malaria Viral-Vectored Vaccines: Investigating Mechanisms of CD8+ T Cell Interference

Forbes

Biswas

Collins

et al. 2011

The Journal of Immunology

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“…A major concern for the development of multivalent vaccines is the potential for vaccine interference that would be associated with poor immune response (29). This effect has been reported using combinations of recombinant proteins (PyMSP-1 42 and PyMSP-8 [25] or PfMSP-1 42 and PfAMA-1 [17]) or using viral vectors combining PyCSP and PyMSP-1 42 (13). In these models, reduced antibody or CD8 ϩ T cell responses suggest a potential adverse interaction that would preclude the use of MSP-1 as a component of a multiantigen vaccine (25).…”

Section: Fig 6 Effects Of Cd4mentioning

confidence: 99%

A Hybrid Multistage Protein Vaccine Induces Protective Immunity against Murine Malaria

et al. 2012

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We have previously reported the design and expression of chimeric recombinant proteins as an effective platform to deliver malaria vaccines. The erythrocytic and exoerythrocytic protein chimeras described included autologous T helper epitopes genetically linked to defined B cell epitopes. Proof-of-principle studies using vaccine constructs based on the Plasmodium yoelii circumsporozoite protein (CSP) and P. yoelii merozoite surface protein-1 (MSP-1) showed encouraging results when tested individually in this mouse malaria model. To evaluate the potential synergistic or additive effect of combining these chimeric antigens, we constructed a synthetic gene encoding a hybrid protein that combined both polypeptides in a single immunogen. The multistage vaccine was expressed in soluble form in Escherichia coli at high yield. Here we report that the multistage protein induced robust immune responses to individual components, with no evidence of vaccine interference. Passive immunization using purified IgG from rabbits immunized with the hybrid protein conferred more robust protection against the experimental challenge with P. yoelii sporozoites than passive immunization with purified IgG from rabbits immunized with the individual proteins. High antibody titers and high frequencies of CD4 ؉ -and CD8 ؉ -specific cytokine-secreting T cells were elicited by vaccination. T cells were multifunctional and able to simultaneously produce interleukin-2 (IL-2), gamma interferon (IFN-␥), and tumor necrosis factor alpha (TNF-␣). The mechanism of vaccine-induced protection involved neutralizing antibodies and effector CD4؉ T cells and resulted in the control of hyperparasitemia and protection against malarial anemia. These data support our strategy of using an array of autologous T helper epitopes to maximize the response to multistage malaria vaccines. M alaria remains a major public health problem, even though the implementation of control measures has significantly reduced the overall transmission in the past few years (32). Parasites of the genus Plasmodium are responsible for an estimated 216 million clinical cases and over a half million deaths annually worldwide (32). The spread of multidrug-resistant strains of parasites has emphasized the need for developing novel intervention measures. Several vaccine candidates mainly focused on Plasmodium falciparum are in different phases of clinical development. Among them, RTS,S/AS02, an adjuvanted fusion protein based on the circumsporozoite protein, has reached phase 3 clinical trials (4). However, the prospect of developing a highly effective multistage vaccine that includes more than a single antigen has not been pursued vigorously.The multistage life cycle of Plasmodium and the intricate hostparasite interactions during the course of malaria infection support the idea of targeting several antigens simultaneously for vaccine development. We have developed several chimeric recombinant proteins for proof-of-principle studies to test the feasibility of developing effective multistage...

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“…A vaccine that can reduce the human toll would be a valuable resource in the fight against malaria. A number of subunit vaccine candidates have been proposed and tested, some with encouraging results (Ellis et al 2009;Pichyangkul et al 2009). For the asexual blood stage, one of the highly regarded candidate antigens is the 19-kDa C-terminal fragment of merozoite surface protein 1 (MSP1 19 ) (Daly and Long 1993;Hirunpetcharat et al 1997;Mazumdar et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Production, characterisation and immunogenicity of a plant-made Plasmodium antigen—the 19 kDa C-terminal fragment of Plasmodium yoelii merozoite surface protein 1

Chung

Wang

Webster

et al. 2011

Appl Microbiol Biotechnol

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Development of a safe, effective and affordable malaria vaccine is central to global disease control efforts. One of the most highly regarded proteins for inclusion in an asexual blood stage subunit vaccine is the 19-kDa C-terminal fragment of merozoite surface protein 1 (MSP1(19)). As production of vaccine antigens in plants can potentially overcome cost and delivery hurdles, we set out to produce MSP1(19) in plants, characterise the protein and test its immunogenicity using a mouse model. Plasmodium yoelii MSP1(19) (PyMSP1(19)) was produced in Nicotiana benthamiana using the MagnICON® deconstructed TMV-based viral vector. PyMSP1(19) yield of at least 23% total soluble protein (TSP;3-4 mg/g Fwt) were achieved using a codon-optimised construct that was targeted to the apoplast. Freeze-dried leaf powder contained at least 20 mg PyMSP1(19) per gram dry weight and the protein retained immunogenicity in this form for more than 2 years. Characterisation studies, including SDS-PAGE, mass spectrometry and circular dichroism, indicated that the plant-expressed PyMSP1(19) was similar to its Escherichia coli- and Saccharomyces cerevisiae-expressed counterparts. Purified plant-made PyMSP1(19) induced strong immune responses following intraperitoneal immunisation, although titres were lower than those induced by an equivalent dose of purified E. coli-expressed PyMSP1(19). The reason for this is uncertain but may be due to differences in the oligomerisation profile of the vaccines. The plant-made PyMSP1(19) vaccine was also found to be orally immunogenic when delivered alone or following immunisation with a PyMSP1(19) DNA vaccine. This study adds to an increasing body of research supporting the feasibility of plants as both a factory for the production of malaria antigens, and as a safe and affordable platform for oral delivery of a temperature-stable malaria vaccine.

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Evaluation of the safety and immunogenicity of Plasmodium falciparum apical membrane antigen 1, merozoite surface protein 1 or RTS,S vaccines with adjuvant system AS02A administered alone or concurrently in rhesus monkeys

Cited by 33 publications

References 61 publications

Combining Liver- and Blood-Stage Malaria Viral-Vectored Vaccines: Investigating Mechanisms of CD8+ T Cell Interference

Combining Liver- and Blood-Stage Malaria Viral-Vectored Vaccines: Investigating Mechanisms of CD8+ T Cell Interference

A Hybrid Multistage Protein Vaccine Induces Protective Immunity against Murine Malaria

Production, characterisation and immunogenicity of a plant-made Plasmodium antigen—the 19 kDa C-terminal fragment of Plasmodium yoelii merozoite surface protein 1

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