Ellis, RD, Mullen, GE, Pierce, M, Martin, LB, Miura, K, Fay, MP et al.. A Phase 1 study of the blood-stage malaria vaccine candidate AMA1-C1/Alhydrogel with CPG 7909, using two different formulations and dosing intervals. Vaccine 27: 4104-4109

Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook I, MD 20852, USA.
Vaccine (Impact Factor: 3.62). 06/2009; 27(31):4104-9. DOI: 10.1016/j.vaccine.2009.04.077
Source: PubMed

ABSTRACT A Phase 1 study was conducted in 24 malaria naïve adults to assess the safety and immunogenicity of the recombinant protein vaccine apical membrane antigen 1-Combination 1 (AMA1-C1)/Alhydrogel with CPG 7909 in two different formulations (phosphate buffer and saline), and given at two different dosing schedules, 0 and 1 month or 0 and 2 months. Both formulations were well tolerated and frequency of local reactions and solicited adverse events was similar among the groups. Peak antibody levels in the groups receiving CPG 7909 in saline were not significantly different than those receiving CPG 7909 in phosphate. Peak antibody levels in the groups vaccinated at a 0,2 month interval were 2.52-fold higher than those vaccinated at a 0,1 month interval (p=0.037, 95% CI 1.03, 4.28). In vitro growth inhibition followed the antibody level: median inhibition was 51% (0,1 month interval) versus 85% (0,2 month interval) in antibody from samples taken 2 weeks post-second vaccination (p=0.056).

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Available from: Greg Mullen, Sep 28, 2015
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    • "The combination of Al(OH) 3 and a CpG oligodeoxynucleotide (CpG) that activates via TLR9 can enhance antibody titers 10-fold or more over either adjuvant alone in mice [14]. In humans, CpG combined with Al(OH) 3 enhanced antibody titers against four different antigens by at least 5-fold compared to Al(OH) 3 as sole adjuvant,[15] [16] [17] [18] and, in one study where it was evaluated, also significantly enhanced antibody affinity[19]. Herein, we describe our findings in mice and monkeys testing the ability of CpG to enhance anti-nicotine antibody functionality induced in response to a model anti-nicotine vaccine comprised of trans-3′ aminomethylnicotine conjugated to diphtheria toxoid (3′AmNic-DT) as antigen and Al(OH) 3 as adjuvant. "
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    • "While they may reduce the parasite load of individuals living in endemic areas, they do not mediate sterile protection or total suppression of parasites in the blood (Genton et al., 2002). Recently, an apical merozoite antigen (AMA)-1 based vaccine that induces high antibody titers, and high GIA responses in vitro in human vaccinees (Ellis et al., 2009) was evaluated for its protective effect in a blood challenge. To this end, the vaccinees were immunized and then challenged with blood infected with the 3D7 parasite clone. "
    Malaria Parasites, 03/2012; , ISBN: 978-953-51-0326-4
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    • "Bc activation and proliferation can also be induced by CpG acting through Toll-like receptor 9 (TLR-9). TLR-9 agonists improve production of antibody by Bc responding to vaccine12, and are in clinical trials as vaccine adjuvants13. We have previously shown that a combination of CpG2008 ODN and cytokines (IL-2, IL-10, IL-15, and BAFF) can induce in vitro mBc differentiation into CD138+ plasma cells9. "
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