title: Safety and immunogenicity of a mutagenized, live attenuated Rift Valley fever vaccine, MP-12, in a Phase 1 dose escalation and route comparison study in humans.
abstract: Rift Valley fever (RVF) poses a risk as a potential agent in bioterrorism or agroterrorism. A live attenuated RVF vaccine (RVF MP-12) has been shown to be safe and protective in animals and showed promise in two initial clinical trials. In the present study, healthy adult human volunteers (N=56) received a single injection of (a) RVF MP-12, administered subcutaneously (SQ) at a concentration of 10(4.7) plaque-forming units (pfu) (SQ Group); (b) RVF MP-12, administered intramuscularly (IM) at 10(3.4)pfu (IM Group 1); (c) RVF MP-12, administered IM at 10(4.4)pfu (IM Group 2); or (d) saline (Placebo Group). The vaccine was well tolerated by volunteers in all dose and route groups. Infrequent and minor adverse events were seen among recipients of both placebo and RVF MP-12. One subject had viremia detectable by direct plaque assay, and six subjects from IM Group 2 had transient low-titer viremia detectable only by nucleic acid amplification. Of the 43 vaccine recipients, 40 (93%) achieved neutralizing antibodies (measured as an 80% plaque reduction neutralization titer [PRNT80]) as well as RVF-specific IgM and IgG. The highest peak geometric mean PRNT80 titers were observed in IM Group 2. Of 34 RVF MP-12 recipients available for testing 1 year following inoculation, 28 (82%) remained seropositive (PRNT80≥1:20); this included 20 of 23 vaccinees (87%) from IM Group 2. The live attenuated RVF MP-12 vaccine was safe and immunogenic at the doses and routes studied. Given the need for an effective vaccine against RVF virus, further evaluation in humans is warranted.
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, United States. Electronic address: phillip.r.pittman.civ@mail.mil.
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Pittman
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, United States.
authors.forename: David
authors.initials: D
authors.lastname: McClain
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, United States.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Quinn
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, United States.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Coonan
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Mangiafico
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, United States.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Makuch
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, United States.
authors.forename: John
authors.initials: J
authors.lastname: Morrill
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, United States.
authors.forename: Clarence J
authors.initials: CJ
authors.lastname: Peters
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007273:Injections, Intramuscular; D008297:Male; D012295:Rift Valley Fever / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D014765:Viral Vaccines / Q000008:administration & dosage*; D014766:Viremia / Q000175:diagnosis; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
keywords: Clinical trial; MP-12; Rift Valley fever; Vaccine