Enhancement of functional antibody responses to AMA1-C1/Alhydrogel®, a Plasmodium falciparum malaria vaccine, with CpG oligodeoxynucleotide

Mullen, Gregory; Giersing, Birgitte; Ajose-Popoola, Olubunmi; Davis, Heather L.; Kothe, Cheryl; Zhou, Hong; Aebig, Joan; Dobrescu, G; Saul, Allan; Long, Carole A.

doi:10.1016/j.vaccine.2005.12.034

Cited by 52 publications

(52 citation statements)

References 36 publications

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“…In our previous study, the addition of the TLR9 agonist CPG 7909 to the AMA1-C1/Alhydrogel formulation greatly increased the functional antibody responses in mice, rats and guinea pigs, and a mixed Th1/Th2 response was observed [10]. A strong positive correlation between GIA activity and anti-AMA1 specific antibody levels was displayed.…”

Section: Introductionmentioning

confidence: 81%

“…For the formulations with CPG 7909, the vaccine proteins were first formulated on Alhydrogel followed by the addition of CPG 7909 to the formulation [10,13,14]. Animal studies were conducted in compliance with the National Institutes of Health guidelines and with an Animal Care and Use Committee-approved protocol.…”

Section: Formulation and Animal Immunizationmentioning

confidence: 99%

“…The antigen concentrations of AMA1 and Pfs25 within the conjugates were calculated based on the amino acid analysis of the conjugate. Comparison of antibody responses between the formulations with or without CPG 7909 was only performed with the 0.03 μg dose for the AMA1-rEPA conjugate, which is considered to be the middle of the dose response curve for AMA1/Alhydrogel, AMA1/Alhydrogel + CPG and AMA1-rEPA/Alhydrogel [7,10]. For the Pfs25-rEPA conjugate, this comparison was evaluated at two doses, 0.05 and 0.25 μg, as the exact middle of the dose response curve was not known.…”

Section: Formulation and Animal Immunizationmentioning

confidence: 99%

“…ELISA was performed following the standardized protocol used in the laboratory [10]. Experimental serum samples and anti-AMA1-FVO or anti-Pfs25 mouse reference standards were used as primary antibodies; alkaline phosphatase-labeled goat anti-mouse IgG (Kirkegaard & Perry Laboratories Inc., Gaithersburg, MD) was used as secondary antibody.…”

Section: Enzyme-linked Immunosorbent Assay and Igg Subclass Analysismentioning

confidence: 99%

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Addition of CpG ODN to recombinant Pseudomonas aeruginosa ExoProtein A conjugates of AMA1 and Pfs25 greatly increases the number of responders

Qian

Rausch

Muratova

et al. 2008

Vaccine

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Both the blood stage protein apical membrane antigen 1 (AMA1) and the 25 kDa sexual stage protein (Pfs25) of Plasmodium falciparum are two leading candidates in malarial vaccine development. We have previously demonstrated that conjugation of these malarial antigens to recombinant Pseudomonas aeruginosa ExoProtein A (rEPA) significantly increased the mean specific functional antibody responses in mice; however, some mice responded poorly and were unable to demonstrate a functional response. We hypothesized that the immunogenicities of these two malarial antigens could be further enhanced by inclusion of a CpG oligodeoxynucleotide in the formulation. Mice were immunized with either rEPA conjugated or unconjugated AMA1 and Pfs25 formulated on Alhydrogel with or without the addition of CPG 7909. Mice received the formulations on days 0 and 28, and mouse sera were collected on day 42. ELISA analyses on these sera showed that the addition of CPG 7909 to AMA1-rEPA and Pfs25-rEPA formulated on Alhydrogel induced significantly higher mean antibody titers than the formulations without CPG 7909, and led to a mixed Th1/Th2 response as demonstrated by the production of mouse IgG1 and IgG2a subclasses. The presence of CPG 7909 in the formulations of both conjugated antigens greatly increased the proportion of responders with antibody titers sufficient to inhibit blood-stage parasite growth in vitro or block transmission of sexual stage parasites to mosquitoes. The results obtained in this study indicate the potential use of a combination strategy to increase the number of responders to malarial antigens in humans.

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Section: Introductionmentioning

confidence: 81%

Section: Formulation and Animal Immunizationmentioning

confidence: 99%

Section: Formulation and Animal Immunizationmentioning

confidence: 99%

Section: Enzyme-linked Immunosorbent Assay and Igg Subclass Analysismentioning

confidence: 99%

See 2 more Smart Citations

Addition of CpG ODN to recombinant Pseudomonas aeruginosa ExoProtein A conjugates of AMA1 and Pfs25 greatly increases the number of responders

Qian

Rausch

Muratova

et al. 2008

Vaccine

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“…Multi-allele and multi-antigen malaria vaccine approaches have shown potential in inducing antibody responses with broad-strain inhibitory capacity in a number of rodent and rabbit studies [33,34,40]. In the current study, the immunological benefits of such immunization strategies, as well as the safety of these formulations, were further analysed in a non-human primate model.…”

Section: Discussionmentioning

confidence: 99%

Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

Kusi

Remarque

Riasat

et al. 2011

Malar J

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BackgroundIncreasing the breadth of the functional antibody response through immunization with Plasmodium falciparum apical membrane antigen 1 (PfAMA1) multi-allele vaccine formulations has been demonstrated in several rodent and rabbit studies. This study assesses the safety and immunogenicity of three PfAMA1 Diversity-Covering (DiCo) vaccine candidates formulated as an equimolar mixture (DiCo mix) in CoVaccine HT™ or Montanide ISA 51, as well as that of a PfAMA1-MSP119 fusion protein formulated in Montanide ISA 51.MethodsVaccine safety in rhesus macaques was monitored by animal behaviour observation and assessment of organ and systemic functions through clinical chemistry and haematology measurements. The immunogenicity of vaccine formulations was assessed by enzyme-linked immunosorbent assays and in vitro parasite growth inhibition assays with three culture-adapted P. falciparum strains.ResultsThese data show that both adjuvants were well tolerated with only transient changes in a few of the chemical and haematological parameters measured. DiCo mix formulated in CoVaccine HT™ proved immunologically and functionally superior to the same candidate formulated in Montanide ISA 51. Immunological data from the fusion protein candidate was however difficult to interpret as four out of six immunized animals were non-responsive for unknown reasons.ConclusionsThe study highlights the safety and immunological benefits of DiCo mix as a potential human vaccine against blood stage malaria, especially when formulated in CoVaccine HT™, and adds to the accumulating data on the specificity broadening effects of DiCo mix.

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A comparative study of the antigen‐specific immune response induced by co‐delivery of CpG ODN and antigen using fusion molecules or biodegradable microparticles**Xue‐Qing Zhang and Christopher E. Dahle contributed equally to this work.

Zhang

Dahle

Weiner

et al. 2007

Journal of Pharmaceutical Sciences

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Enhancement of functional antibody responses to AMA1-C1/Alhydrogel®, a Plasmodium falciparum malaria vaccine, with CpG oligodeoxynucleotide

Cited by 52 publications

References 36 publications

Addition of CpG ODN to recombinant Pseudomonas aeruginosa ExoProtein A conjugates of AMA1 and Pfs25 greatly increases the number of responders

Addition of CpG ODN to recombinant Pseudomonas aeruginosa ExoProtein A conjugates of AMA1 and Pfs25 greatly increases the number of responders

Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

A comparative study of the antigen‐specific immune response induced by co‐delivery of CpG ODN and antigen using fusion molecules or biodegradable microparticles**Xue‐Qing Zhang and Christopher E. Dahle contributed equally to this work.

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