title: Rift Valley fever MP-12 vaccine Phase 2 clinical trial: Safety, immunogenicity, and genetic characterization of virus isolates.
abstract: An outbreak or deliberate release of Rift Valley fever (RVF) virus could have serious public health and socioeconomic consequences. A safe RVF vaccine capable of eliciting long-lasting immunity after a single injection is urgently needed. The live attenuated RVF MP-12 vaccine candidate has shown promise in Phase 1 clinical trials; no evidence of reversion to virulence has been identified in numerous animal studies. The objective of this Phase 2 clinical trial was to (a) further examine the safety and immunogenicity of RVF MP-12 in RVF virus-naïve humans and (b) characterize isolates of RVF MP-12 virus recovered from the blood of vaccinated subjects to evaluate the genetic stability of MP-12 attenuation. We found that RVF MP-12 was well tolerated, causing mostly mild reactions that resolved without sequelae. Of 19 subjects, 18 (95%) and 19 (100%) achieved, respectively, 80% and 50% plaque reduction neutralization titers (PRNT80 and PRNT50)≥1:20 by postvaccination day 28. All 18 PRNT80 responders maintained PRNT80 and PRNT50≥1:40 until at least postvaccination month 12. Viremia was undetectable in the plasma of any subject by direct plaque assay techniques. However, 5 of 19 vaccinees were positive for MP-12 isolates in plasma by blind passage of plasma on Vero cells. Vaccine virus was also recovered from buffy coat material from one of those vaccinees and from one additional vaccinee. Through RNA sequencing of MP-12 isolates, we found no reversions of amino acids to those of the parent virulent virus (strain ZH548). Five years after a single dose of RVF MP-12 vaccine, 8 of 9 vaccinees (89%) maintained a PRNT80≥1:20. These findings support the continued development of RVF MP-12 as a countermeasure against RVF virus in humans.
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, Frederick, 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, Frederick, MD 21702-5011, United States.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Norris
authors.affiliation: ClinicalRM, USAMRIID, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, United States.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Brown
authors.affiliation: Goldbelt Raven LLC, USAMRIID, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, United States.
authors.forename: Manmohan V
authors.initials: MV
authors.lastname: Ranadive
authors.affiliation: Goldbelt Raven LLC, USAMRIID, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, United States.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Schibly
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, United States.
authors.forename: George E
authors.initials: GE
authors.lastname: Bettinger
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, United States.
authors.forename: Nandadeva
authors.initials: N
authors.lastname: Lokugamage
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, United States.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Korman
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, United States.
authors.forename: John C
authors.initials: JC
authors.lastname: Morrill
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, United States.
authors.forename: Clarence J
authors.initials: CJ
authors.lastname: Peters
mesh_terms: D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D005260:Female; D042822:Genomic Instability; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009500:Neutralization Tests; D012295:Rift Valley Fever / Q000517:prevention & control*; D012296:Rift Valley fever virus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D014709:Vero Cells; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D014774:Virulence; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
keywords: Clinical trial; MP-12; Rift Valley fever; Vaccine