A Modified Hepatitis B Virus Core Particle Containing Multiple Epitopes of the<i>Plasmodium falciparum</i>Circumsporozoite Protein Provides a Highly Immunogenic Malaria Vaccine in Preclinical Analyses in Rodent and Primate Hosts

Birkett, Ashley; Lyons, Katie; Schmidt, Annette; Boyd, David A.; Oliveira, Giane A.; Siddique, Abu Bakar; Nussenzweig, Ruth S.; Calvo‐Calle, J. Mauricio; Nardin, Elizabeth

doi:10.1128/iai.70.12.6860-6870.2002

Cited by 78 publications

(57 citation statements)

References 51 publications

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“…Generally, c/e1 insertions were more immunogenic than terminal additions; recent examples include CLP carrying B and T cell epitopes from Plasmodium falciparum [31,32] and fragments of the hantavirus nucleocapsid protein [33]. However, since the particle-forming ability of such fusion proteins frequently decreased with increasing insert size, the c/e1 loop was thought to have a limited insertion capacity.…”

Section: Introductionmentioning

confidence: 99%

A fusion product of the complete Borrelia burgdorferi outer surface protein A (OspA) and the hepatitis B virus capsid protein is highly immunogenic and induces protective immunity similar to that seen with an effective lipidated OspA vaccine formula

et al. 2005

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The immunogenicity of peptides and protein fragments can be considerably enhanced by their presentation on particulate carriers such as capsid‐like particles (CLP) from hepatitis B virus (HBV). Here we tested the suitability of the HBV capsid protein as a carrier for a relevant full‐length pathogen‐derived protein antigen. The entire 255‐amino acid ectodomain of the outer surface protein A (OspA) from Borrelia burgdorferi, the causative agent of Lyme disease, was inserted into the major B cell epitope of the HBV capsid, yielding a multimerization‐competent fusion protein, termed coreOspA. CoreOspA, consisting only in part of regular CLP, induced antibodies to OspA, including the Ig isotype profile and specificity for the protective epitope LA‐2, with an efficiency similar to that of recombinant lipidated OspA, the first generation vaccine against Lyme disease. Moreover, coreOspA actively and passively protected mice against subsequent challenge with B. burgdorferi. The data demonstrate the capacity of the HBV capsid protein to act as a potent immunomodulator even for full‐length and structurally complex polypeptide chains and thus opens new avenues for novel vaccine designs.

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Section: Introductionmentioning

confidence: 99%

A fusion product of the complete Borrelia burgdorferi outer surface protein A (OspA) and the hepatitis B virus capsid protein is highly immunogenic and induces protective immunity similar to that seen with an effective lipidated OspA vaccine formula

et al. 2005

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“…Hybrid particles were expressed and purified as described previously (5). Five or 10 g of CV-1866 was diluted in endotoxin-free PBS and administered i.d or i.p.…”

Section: Animals and Immunizationsmentioning

confidence: 99%

“…Once inside hepatocytes, the same antigen can be targeted by protective T cells that then destroy the infected cell (20). Vaccines designed to induce anti-CSP antibodies (5,17,27,38,47) or CD8 ϩ T cells (3,16,37) have demonstrated some protection against malaria infection in rodent models.…”

mentioning

confidence: 99%

Combination of Protein and Viral Vaccines Induces Potent Cellular and Humoral Immune Responses and Enhanced Protection from Murine Malaria Challenge

Hutchings

Birkett²,

Moore

et al. 2007

Infect Immun

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The search for an efficacious vaccine against malaria is ongoing, and it is now widely believed that to confer protection a vaccine must induce very strong cellular and humoral immunity concurrently. We studied the immune response in mice immunized with the recombinant viral vaccines fowlpox strain FP9 and modified virus Ankara (MVA), a protein vaccine (CV-1866), or a combination of the two; all vaccines express parts of the same preerythrocytic malaria antigen, the Plasmodium berghei circumsporozoite protein (CSP). Mice were then challenged with P. berghei sporozoites to determine the protective efficacies of different vaccine regimens. Two immunizations with the protein vaccine CV-1866, based on the hepatitis B core antigen particle, induced strong humoral immunity to the repeat region of CSP that was weakly protective against sporozoite challenge. Prime-boost with the viral vector vaccines, FP9 followed by MVA, induced strong T-cell immunity to the CD8 ؉ epitope Pb9 and partially protected animals from challenge. Physically mixing CV-1866 with FP9 or MVA and then immunizing with the resultant combinations in a prime-boost regimen induced both cellular and humoral immunity and afforded substantially higher levels of protection (combination, 90%) than either vaccine alone (CV-1866, 12%; FP9/MVA, 37%). For diseases such as malaria in which different potent immune responses are required to protect against different stages, using combinations of partially effective vaccines may offer a more rapid route to achieving deployable levels of efficacy than individual vaccine strategies.

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“…ICC-1132 administered in water-in-oil adjuvants, such as Freund's adjuvant or Montanide ISA 720, was significantly more immunogenic than alum formulations in preclinical studies in mice and monkeys (3). Antirepeat antibody titers of Ͼ1 ϫ 10 6 were elicited by ICC-1132 in Montanide ISA 720, while alum formulations elicited titers that were 1 to 2 log units lower.…”

mentioning

confidence: 99%

“…In recent preclinical studies, an Escherichia coli-expressed HBc VLP containing P. falciparum CS epitopes, designated ICC-1132, elicited high levels of humoral and cellular immunity in mice and monkeys when formulated in adjuvants suitable for human use (3,4,17). The ICC-1132 vaccine candidate contains the immunodominant B-cell epitope, (NANP) 3, and a T-helper epitope termed T1, NANPNVDPNANP, from the conserved central repeat region of the CS protein (Fig.…”

mentioning

confidence: 99%

Safety and Enhanced Immunogenicity of a Hepatitis B Core ParticlePlasmodium falciparumMalaria Vaccine Formulated in Adjuvant Montanide ISA 720 in a Phase I Trial

Oliveira

Wetzel²,

Calvo‐Calle

et al. 2005

Infect Immun

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Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses. In a previous phase I trial, an alum formulation of ICC-1132, a malaria vaccine candidate comprising hepatitis B core (HBc) virus-like particle containing Plasmodium falciparum circumsporozoite (CS) protein epitopes, was shown to elicit Plasmodium falciparum-specific antibody and cellular responses.

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A Modified Hepatitis B Virus Core Particle Containing Multiple Epitopes of thePlasmodium falciparumCircumsporozoite Protein Provides a Highly Immunogenic Malaria Vaccine in Preclinical Analyses in Rodent and Primate Hosts

Cited by 78 publications

References 51 publications

A fusion product of the complete Borrelia burgdorferi outer surface protein A (OspA) and the hepatitis B virus capsid protein is highly immunogenic and induces protective immunity similar to that seen with an effective lipidated OspA vaccine formula

A fusion product of the complete Borrelia burgdorferi outer surface protein A (OspA) and the hepatitis B virus capsid protein is highly immunogenic and induces protective immunity similar to that seen with an effective lipidated OspA vaccine formula

Combination of Protein and Viral Vaccines Induces Potent Cellular and Humoral Immune Responses and Enhanced Protection from Murine Malaria Challenge

Safety and Enhanced Immunogenicity of a Hepatitis B Core ParticlePlasmodium falciparumMalaria Vaccine Formulated in Adjuvant Montanide ISA 720 in a Phase I Trial

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