Journal Article

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

2016

Overview

•A single dose of RVF MP-12 vaccine, delivered intramuscularly or subcutaneously, was well tolerated by human volunteers.•Low-titer viremia was detected via amplification in six subjects and via direct plaque assay in one subject.•Over the course of the study, 93% of vaccinees (40 of 43) achieved neutralizing antibodies and RVF-specific IgM and IgG.•Among vaccinees tested 1 year after vaccination, 82% remained seropositive. 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.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adult / adults / Allergy and Immunology / Antibodies, Neutralizing - blood / Antibodies, Viral - blood / Armed forces / Bioterrorism / Clinical trial / clinical trials / Cloning / Dose-Response Relationship, Immunologic / Family medical history / Female / Fever / gene amplification / Headaches / Humans / immune response / Immunization / Immunogenicity / immunoglobulin G / Immunoglobulin G - blood / immunoglobulin M / Immunoglobulin M - blood / Injections, Intramuscular / Laboratories / Male / Mortality / MP-12 / Mutagenesis / Neutralization / neutralizing antibodies / Nucleic acids / Rift Valley fever / Rift Valley Fever - prevention & control / risk / seroprevalence / Sheep / Vaccine / Vaccines / Vaccines, Attenuated - administration & dosage / Vector-borne diseases / Viral Vaccines - administration & dosage / viremia / Viremia - diagnosis / viruses / volunteers / Young Adult