TY - JOUR
T1 - Safety and immunogenicityof Pfs25-EPA/ alhydrogel1, a transmission blocking vaccine against Plasmodium falciparum
T2 - An open label study in malaria naïve adults
AU - Talaat, Kawsar R.
AU - Ellis, Ruth D.
AU - Hurd, Janet
AU - Hentrich, Autumn
AU - Gabriel, Erin
AU - Hynes, Noreen A.
AU - Rausch, Kelly M.
AU - Zhu, Daming
AU - Muratova, Olga
AU - Herrera, Raul
AU - Anderson, Charles
AU - Jones, David
AU - Aebig, Joan
AU - Brockley, Sarah
AU - MacDonald, Nicholas J.
AU - Wang, Xiaowei
AU - Fay, Michael P.
AU - Healy, Sara A.
AU - Durbin, Anna P.
AU - Narum, David L.
AU - Wu, Yimin
AU - Duffy, Patrick E.
N1 - Funding Information:
The authors would like to thank the participants for volunteering for the study; Sheila Carpenter-Chavis for laboratory assistance, and the members of the LMIV vaccine development units for regulatory and technical support. This research was funded in part by the Intramural Research Program of the NIAID, NIH and by PATH Malaria Vaccine Initiative. PATH Malaria Vaccine Initiative also provided project management support.
PY - 2016/10
Y1 - 2016/10
N2 - Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, doseescalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel1. Thirty malaria-naïve healthy adults received up to four doses of the conjugate vaccine, with 8, 16, or 47 μg of conjugated Pfs25 mass, at 0, 2, 4, and 10 months. Vaccinations were generally well tolerated. The majority of solicited adverse events were mild in severity with pain at the injection site the most common complaint. Anemia was the most common laboratory abnormality, but was considered possibly related to the study in only a minority of cases. No vaccine-related serious adverse events occurred. The peak geometric mean anti-Pfs25 antibody level in the highest dose group was 88 (95% CI 53, 147) μg/mL two weeks after the 4th vaccination, and declined to near baseline one year later. Antibody avidity increased over successive vaccinations. Transmission blocking activity demonstrated in a standard membrane feeding assay (SMFA) also increased from the second to the third dose, and correlated with antibody titer and, after the final dose, with antibody avidity. These results support the further evaluation of Pfs25-EPA/Alhydrogel1 in a malaria-endemic population.
AB - Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, doseescalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel1. Thirty malaria-naïve healthy adults received up to four doses of the conjugate vaccine, with 8, 16, or 47 μg of conjugated Pfs25 mass, at 0, 2, 4, and 10 months. Vaccinations were generally well tolerated. The majority of solicited adverse events were mild in severity with pain at the injection site the most common complaint. Anemia was the most common laboratory abnormality, but was considered possibly related to the study in only a minority of cases. No vaccine-related serious adverse events occurred. The peak geometric mean anti-Pfs25 antibody level in the highest dose group was 88 (95% CI 53, 147) μg/mL two weeks after the 4th vaccination, and declined to near baseline one year later. Antibody avidity increased over successive vaccinations. Transmission blocking activity demonstrated in a standard membrane feeding assay (SMFA) also increased from the second to the third dose, and correlated with antibody titer and, after the final dose, with antibody avidity. These results support the further evaluation of Pfs25-EPA/Alhydrogel1 in a malaria-endemic population.
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U2 - 10.1371/journal.pone.0163144
DO - 10.1371/journal.pone.0163144
M3 - Article
C2 - 27749907
AN - SCOPUS:84992199683
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 10
M1 - e0163144
ER -