Rift Valley fever MP-12 vaccine Phase 2 clinical trial

Safety, immunogenicity, and genetic characterization of virus isolates

Phillip R. Pittman, Sarah L. Norris, Elizabeth S. Brown, Manmohan V. Ranadive, Barbara A. Schibly, George E. Bettinger, Nandadeva Lokugamage, Lawrence Korman, John C. Morrill, Clarence J. Peters

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)523-530
Number of pages8
JournalVaccine
Volume34
Issue number4
DOIs
StatePublished - Jan 20 2016

Fingerprint

Rift Valley Fever
Rift Valley fever
clinical trials
Vaccines
immune response
Clinical Trials
vaccines
Viruses
Safety
Rift Valley fever virus
viruses
RNA Sequence Analysis
Clinical Trials, Phase I
genetic stability
Vero Cells
complications (disease)
Viremia
viremia
neutralization
Disease Outbreaks

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

Pittman, P. R., Norris, S. L., Brown, E. S., Ranadive, M. V., Schibly, B. A., Bettinger, G. E., ... Peters, C. J. (2016). Rift Valley fever MP-12 vaccine Phase 2 clinical trial: Safety, immunogenicity, and genetic characterization of virus isolates. Vaccine, 34(4), 523-530. https://doi.org/10.1016/j.vaccine.2015.11.078

Rift Valley fever MP-12 vaccine Phase 2 clinical trial : Safety, immunogenicity, and genetic characterization of virus isolates. / Pittman, Phillip R.; Norris, Sarah L.; Brown, Elizabeth S.; Ranadive, Manmohan V.; Schibly, Barbara A.; Bettinger, George E.; Lokugamage, Nandadeva; Korman, Lawrence; Morrill, John C.; Peters, Clarence J.

In: Vaccine, Vol. 34, No. 4, 20.01.2016, p. 523-530.

Research output: Contribution to journalArticle

Pittman, PR, Norris, SL, Brown, ES, Ranadive, MV, Schibly, BA, Bettinger, GE, Lokugamage, N, Korman, L, Morrill, JC & Peters, CJ 2016, 'Rift Valley fever MP-12 vaccine Phase 2 clinical trial: Safety, immunogenicity, and genetic characterization of virus isolates', Vaccine, vol. 34, no. 4, pp. 523-530. https://doi.org/10.1016/j.vaccine.2015.11.078
Pittman, Phillip R. ; Norris, Sarah L. ; Brown, Elizabeth S. ; Ranadive, Manmohan V. ; Schibly, Barbara A. ; Bettinger, George E. ; Lokugamage, Nandadeva ; Korman, Lawrence ; Morrill, John C. ; Peters, Clarence J. / Rift Valley fever MP-12 vaccine Phase 2 clinical trial : Safety, immunogenicity, and genetic characterization of virus isolates. In: Vaccine. 2016 ; Vol. 34, No. 4. pp. 523-530.
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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-na{\"i}ve 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.",
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