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

Phillip R. Pittman, David McClain, Xiaofei Quinn, Kevin M. Coonan, Joseph Mangiafico, Richard S. Makuch, John Morrill, Clarence J. Peters

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 104.7 plaque-forming units (pfu) (SQ Group); (b) RVF MP-12, administered intramuscularly (IM) at 103.4pfu (IM Group 1); (c) RVF MP-12, administered IM at 104.4pfu (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.

Original languageEnglish (US)
Pages (from-to)424-429
Number of pages6
JournalVaccine
Volume34
Issue number4
DOIs
StatePublished - Jan 20 2016
Externally publishedYes

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Rift Valley Fever
Rift Valley fever
Vaccines
immune response
vaccines
Safety
dosage
bioterrorism
Viremia
viremia
placebos
volunteers
Volunteers
Rift Valley fever virus
Placebos
Biological Warfare Agents
Neutralizing Antibodies
neutralizing antibodies
neutralization
Nucleic Acids

Keywords

  • Clinical trial
  • MP-12
  • Rift Valley fever
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

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. / Pittman, Phillip R.; McClain, David; Quinn, Xiaofei; Coonan, Kevin M.; Mangiafico, Joseph; Makuch, Richard S.; Morrill, John; Peters, Clarence J.

In: Vaccine, Vol. 34, No. 4, 20.01.2016, p. 424-429.

Research output: Contribution to journalArticle

Pittman, Phillip R. ; McClain, David ; Quinn, Xiaofei ; Coonan, Kevin M. ; Mangiafico, Joseph ; Makuch, Richard S. ; Morrill, John ; Peters, Clarence J. / 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. In: Vaccine. 2016 ; Vol. 34, No. 4. pp. 424-429.
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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 104.7 plaque-forming units (pfu) (SQ Group); (b) RVF MP-12, administered intramuscularly (IM) at 103.4pfu (IM Group 1); (c) RVF MP-12, administered IM at 104.4pfu (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.",
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