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

Kusi KA, Remarque EJ, Riasat V, Walraven V, Thomas AW, Faber BW, Kocken CH - Malar. J. (2011)

Bottom Line: Vaccine safety in rhesus macaques was monitored by animal behaviour observation and assessment of organ and systemic functions through clinical chemistry and haematology measurements.These 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Parasitology, Biomedical Primate Research Centre, Postbox 3306, 2280 GH, Rijswijk, The Netherlands.

ABSTRACT

Background: Increasing 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.

Methods: Vaccine 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.

Results: These 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.

Conclusions: The 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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Related in: MedlinePlus

IgG titres in day 70 sera from all three immunization groups. Anti-PfAMA1 titres in all immunization groups were measured against seven allelic vaccine antigens (DiCo 1, DiCo 2 and DiCo 3 as well as PfAMA1 from the FVO, HB3, 3D7 and CAMP parasite strains) while anti- MSP119 IgG levels in the AM/ISA group were measured against PfMSP119. For each immunization group, plot symbols represent data from individual animals in all panels. Plot symbols are also the same as those used for the same animals in Figure 1.
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Figure 2: IgG titres in day 70 sera from all three immunization groups. Anti-PfAMA1 titres in all immunization groups were measured against seven allelic vaccine antigens (DiCo 1, DiCo 2 and DiCo 3 as well as PfAMA1 from the FVO, HB3, 3D7 and CAMP parasite strains) while anti- MSP119 IgG levels in the AM/ISA group were measured against PfMSP119. For each immunization group, plot symbols represent data from individual animals in all panels. Plot symbols are also the same as those used for the same animals in Figure 1.

Mentions: IgG levels against seven AMA1 alleles and MSP119 at all sampling time points were determined using a harmonized ELISA. The three vaccine formulations induced appreciable levels of antibodies against the tested antigens and titres against all antigens increased in a similar manner and generally peaked on day 70, two weeks after the final vaccine injections were given. IgG titres against the FVO AMA1 allele at all time-points are presented in Figure 1 and day 70 titres against all antigens are presented in Figure 2. Beyond day 70, IgG titres in the two DiCo mix immunization groups showed a decline that was statistically significantly lower on day 126 compared to day 70 levels (p < 0.05 for all AMA1 antigens, Student t test). Both the anti-AMA1 and anti-MSP119 levels for the AM/ISA group were however not significantly different on days 70 and 126 (p > 0.05, Student t test).


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

Kusi KA, Remarque EJ, Riasat V, Walraven V, Thomas AW, Faber BW, Kocken CH - Malar. J. (2011)

IgG titres in day 70 sera from all three immunization groups. Anti-PfAMA1 titres in all immunization groups were measured against seven allelic vaccine antigens (DiCo 1, DiCo 2 and DiCo 3 as well as PfAMA1 from the FVO, HB3, 3D7 and CAMP parasite strains) while anti- MSP119 IgG levels in the AM/ISA group were measured against PfMSP119. For each immunization group, plot symbols represent data from individual animals in all panels. Plot symbols are also the same as those used for the same animals in Figure 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3142537&req=5

Figure 2: IgG titres in day 70 sera from all three immunization groups. Anti-PfAMA1 titres in all immunization groups were measured against seven allelic vaccine antigens (DiCo 1, DiCo 2 and DiCo 3 as well as PfAMA1 from the FVO, HB3, 3D7 and CAMP parasite strains) while anti- MSP119 IgG levels in the AM/ISA group were measured against PfMSP119. For each immunization group, plot symbols represent data from individual animals in all panels. Plot symbols are also the same as those used for the same animals in Figure 1.
Mentions: IgG levels against seven AMA1 alleles and MSP119 at all sampling time points were determined using a harmonized ELISA. The three vaccine formulations induced appreciable levels of antibodies against the tested antigens and titres against all antigens increased in a similar manner and generally peaked on day 70, two weeks after the final vaccine injections were given. IgG titres against the FVO AMA1 allele at all time-points are presented in Figure 1 and day 70 titres against all antigens are presented in Figure 2. Beyond day 70, IgG titres in the two DiCo mix immunization groups showed a decline that was statistically significantly lower on day 126 compared to day 70 levels (p < 0.05 for all AMA1 antigens, Student t test). Both the anti-AMA1 and anti-MSP119 levels for the AM/ISA group were however not significantly different on days 70 and 126 (p > 0.05, Student t test).

Bottom Line: Vaccine safety in rhesus macaques was monitored by animal behaviour observation and assessment of organ and systemic functions through clinical chemistry and haematology measurements.These 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Parasitology, Biomedical Primate Research Centre, Postbox 3306, 2280 GH, Rijswijk, The Netherlands.

ABSTRACT

Background: Increasing 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.

Methods: Vaccine 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.

Results: These 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.

Conclusions: The 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.

Show MeSH
Related in: MedlinePlus