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Vaccine Detail

P. falciparum MSP1 from transgenic mice with Freund's adjuvant
Vaccine Information
  • Vaccine Name: P. falciparum MSP1 from transgenic mice with Freund's adjuvant
  • Target Pathogen: Plasmodium spp.
  • Target Disease: Malaria
  • Vaccine Ontology ID: VO_0000775
  • Type: Subunit vaccine
  • Antigen: the 42-kDa C-terminal portion of Plasmodium falciparum merozoite surface protein 1 (MSP1) (Stowers et al., 2002).
  • MSP-1 gene engineering:
    • Type: Recombinant protein preparation
    • Description: Generated by transgenic mice (Stowers et al., 2002).
    • Detailed Gene Information: Click Here.
  • Adjuvant: complete Freunds adjuvant
    • Adjuvant name: complete Freunds adjuvant
    • VO adjuvant ID: VO_0000139
    • Description: The initial vaccinations were emulsified with complete Freund's adjuvant (Sigma), and the next two with incomplete Freund's adjuvant (Sigma) (Stowers et al., 2002).
  • Adjuvant: incomplete Freunds adjuvant
    • Adjuvant name: incomplete Freunds adjuvant
    • VO adjuvant ID: VO_0000142
    • Description: The initial vaccinations were emulsified with complete Freund's adjuvant (Sigma), and the next two with incomplete Freund's adjuvant (Sigma) (Stowers et al., 2002).
  • Preparation: Two strains of transgenic mice were generated that secrete into their milk a malaria vaccine candidate, the 42-kDa C-terminal portion of Plasmodium falciparum merozoite surface protein 1 (MSP1-42). One strain secretes an MSP1-42 with an amino acid sequence homologous to that of the FVO parasite line. In the other strain, an MSP1-42 where two putative N-linked glycosylation sites in the FVO sequence have been removed. Both forms of MSP142 were purified from whole milk to greater than 91% homogeneity at high yields (Stowers et al., 2002).
  • Virulence: None.
  • Description: It is likely for producing efficacious malarial vaccines in transgenic animals (Stowers et al., 2002).
Host Response

Monkey Response

  • Host Strain: owl monkey (Aotus nancymai)
  • Vaccination Protocol: In total 28 monkeys were randomly assigned to groups of seven. The three vaccine groups received bvMSP1-42, TgMSP1-42 NG, and TgMSP1-42 G, respectively, and the fourth group placebo. Monkeys received three vaccinations of 100 µg of the respective recombinant protein 3 wk apart, following our established protocol. The initial vaccinations were emulsified with complete Freund's adjuvant (Sigma), and the next two with incomplete Freund's adjuvant (Sigma) (Stowers et al., 2002).
  • Immune Response: There was a significant difference in the Endpoint ELISA titers to bvMSP142 between those animals vaccinated with bvMSP142 and TgMSP142 G (P = 0.008), and between those vaccinated with TgMSP142 NG and TgMSP142 G (P = 0.05). No differences in titers were observed between the bvMSP142 and TgMSP142 NG groups. No significant differences were seen in ELISA titers to other antigens (TgMSP142 NG, TgMSP142 G, or MSP119), nor were any significant differences seen in IFA titers against P. falciparum FVO parasites. Overall, antibody titers to none of the four antigens used as ELISA capture antigens (bvMSP142, TgMSP142 NG, TgMSP142 G, or MSP119) correlated with the primary outcome of protection as defined above (cumulative parasitemia until first monkey treated for anemia). However, antibody titers to bvMSP142 did correlate with days until treatment (r2 = 0.6241, P = 0.005) and inversely with parasitemia at time of treatment (r2 = -0.4206, P = 0.05) (Stowers et al., 2002).
  • Side Effects: During vaccination, three animals died (two in the TgMSP142 NG group and one in the TgMSP142 G group), unfortunately not a rare occurrence with these fragile monkeys. No animals died during the second study. When partially protected from P. falciparum malaria, it is a characteristic of Aotus monkeys that some protected animals will suffer from anemia (Stowers et al., 2002).
  • Challenge Protocol: Vaccinated monkeys were challenged 15 days after the third vaccination by i.v. infusion of a freshly passaged preparation of 104 infected RBC of the highly virulent P. falciparum FVO strain. Monkeys were treated when parasitemia reached 5%, or their hematocrit fell below 20%. All monkeys not treated previously were treated on day 30. The treatment consisted of mefloquine administered in a single dose of 25 mg/kg of body mass by intubation. The second Aotus challenge trial followed the protocol outlined above, with the exceptions that only two groups (TgMSP142 NG and placebo) and a larger challenge inoculum were used (1 ml of 5 × 104 pRBCs/ml) (Stowers et al., 2002).
  • Efficacy: Vaccination with the glycosylated version of milk-derived MSP1(42) conferred no protection compared with an adjuvant control. Vaccination with the nonglycosylated, milk-derived MSP1(42) successfully protected the monkeys, with 4/5 animals able to control an otherwise lethal infection with P falciparum compared with 1/7 control animals (Stowers et al., 2002).
  • Description: Analysis of the different vaccines used suggested that the differing nature of the glycosylation patterns may have played a critical role in determining efficacy (Stowers et al., 2002).
References
Stowers et al., 2002: Stowers AW, Chen Lh LH, Zhang Y, Kennedy MC, Zou L, Lambert L, Rice TJ, Kaslow DC, Saul A, Long CA, Meade H, Miller LH. A recombinant vaccine expressed in the milk of transgenic mice protects Aotus monkeys from a lethal challenge with Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America. 2002 Jan 8; 99(1); 339-44. [PubMed: 11752405].