Phase 1 Trial of the Plasmodium falciparum Blood Stage Vaccine MSP142-C1/Alhydrogel with and without CPG 7909 in Malaria Naïve Adults

PLoS One

Michael P. Fay¹  Donna Shaffer²  Anna P. Durbin²  Carole A. Long³  Ruth D. Ellis⁴  Kazutoyo Miura⁴  Daming Zhu⁴  Laura B. Martin⁴  Gregory E. D. Mullen⁴  Siddhartha Mahanty⁴  Louis H. Miller⁴  David L. Narum⁴ 

[1] Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Rockville, Maryland, United States of America;Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America;Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Rockville, Maryland, United States of America;Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Rockville, Maryland, United States of America

关键词: Vaccination and immunization;    Treatment guidelines;    Vaccines;    Antibodies;    Adverse events;    Malaria;    Antibody response;    Immunologic adjuvants;   

DOI  :  10.1371/journal.pone.0008787

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background Merozoite surface protein 142 (MSP142) is a leading blood stage malaria vaccine candidate. In order to induce immune responses that cover the major antigenic polymorphisms, FVO and 3D7 recombinant proteins of MSP142 were mixed (MSP142-C1). To improve the level of antibody response, MSP142-C1 was formulated with Alhydrogel plus the novel adjuvant CPG 7909.Methods A Phase 1 clinical trial was conducted in healthy malaria-naïve adults at the Center for Immunization Research in Washington, D.C., to evaluate the safety and immunogenicity of MSP142-C1/Alhydrogel +/− CPG 7909. Sixty volunteers were enrolled in dose escalating cohorts and randomized to receive three vaccinations of either 40 or 160 µg protein adsorbed to Alhydrogel +/− 560 µg CPG 7909 at 0, 1 and 2 months.Results Vaccinations were well tolerated, with only one related adverse event graded as severe (Grade 3 injection site erythema) and all other vaccine related adverse events graded as either mild or moderate. Local adverse events were more frequent and severe in the groups receiving CPG. The addition of CPG enhanced anti-MSP142 antibody responses following vaccination by up to 49-fold two weeks after second immunization and 8-fold two weeks after the third immunization when compared to MSP142-C1/Alhydrogel alone (p<0.0001). After the third immunization, functionality of the antibody was tested by an in vitro growth inhibition assay. Inhibition was a function of antibody titer, with an average of 3% (range −2 to 10%) in the non CPG groups versus 14% (3 to 32%) in the CPG groups.Conclusion/Significance The favorable safety profile and high antibody responses induced with MSP142-C1/Alhydrogel + CPG 7909 are encouraging. MSP142-C1/Alhydrogel is being combined with other blood stage antigens and will be taken forward in a formulation adjuvanted with CPG 7909.Trial Registration ClinicalTrials.gov Identifier: NCT00320658.

【 授权许可】

CC BY