Randomized, placebo-controlled trial to assess the safety and immunogenicity of an adenovirus type 35-based circumsporozoite malaria vaccine in healthy adults.

Creech CB, Dekker CL, Ho D, Phillips S, Mackey S, Murray-Krezan C, Grazia Pau M, Hendriks J, Brown V, Dally LG, Versteege I, Edwards KM
Hum Vaccin Immunother. 2013 9 (12): 2548-57

PMID: 23955431 · PMCID: PMC4162066 · DOI:10.4161/hv.26038

Malaria results in over 650,000 deaths each year; thus, there is an urgent need for an effective vaccine. Pre-clinical studies and recently reported human trials suggest that pre-erythrocytic stage vaccines can provide protection against infection. A Phase 1, randomized, placebo-controlled, dose-escalation study was conducted with a vaccine composed of a replication-deficient adenovirus-35 backbone with P. falciparum circumsporozoite (CS) surface antigen (Ad35.CS.01). Healthy adult subjects received three doses of 10 (8), 10 (9), 10 (10), or 10 (11) vp/mL Ad35.CS.01 vaccine or saline placebo intramuscularly at 0, 1, and 6-mo intervals. Adverse events were assessed and anti-CS antibody responses were determined by ELISA. Seventy-two individuals were enrolled, with age, gender, and ethnicity similar across each study arm. While the vaccine was generally well tolerated, adverse events were more frequent in the highest dose groups (10 (10) and 10 (11) vp/mL). More robust humoral responses were also noted at the highest doses, with 73% developing a positive ELISA response after the three dose series of 10 (11) vp/mL. The Ad35.CS.01 vaccine was most immunogenic at the highest dosages (10 (10) and 10 (11) vp/mL). Reactogenicity findings were more common after the 10 (11) vp/mL dose, although most were mild or moderate in nature and resolved without therapy.

MeSH Terms (20)

Adenoviruses, Human Adolescent Adult Antibodies, Protozoan Antigens, Protozoan Drug-Related Side Effects and Adverse Reactions Drug Carriers Enzyme-Linked Immunosorbent Assay Female Genetic Vectors Humans Malaria Malaria Vaccines Middle Aged Placebos Protozoan Proteins Treatment Outcome Vaccination Vaccines, Synthetic Young Adult

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