Safety and Immunogenicity of Two Novel Type 2 Oral Poliovirus Vaccine Candidates Compared With Monovalent Type 2 Oral Poliovirus Vaccine in Children and Infants: Two Clinical Trials

Abstract

There is an increasing incidence of paralytic poliomyelitis cases because of circulating vaccine-derived polioviruses over the past 3 years. The person-to-person transmission of circulating vaccine-derived polioviruses that are neurovirulent are primarily responsible for this emergence of these outbreaks; the World Health Organization has designated type 2 circulating vaccine-derived polioviruses as a Public Health Emergency of International Concern.Two novel oral poliovirus vaccines (OPVs), OPV2-c1 and OPV2-c2, were tested for safety and immunogenicity in infants and children. These 2 novel poliovirus vaccines had genetic modifications introduced to enhance the stability of the Sabin attenuations and reduce the risk of reversion to neurovirulence. A previous study in healthy adults was conducted.This study was a phase 2 study with low and high doses of 2 novel OPV2 candidates in Panama through a multicenter, partly masked randomized study. In the phase 2 study, children received 2 high doses of novel OPV2-c1 or novel OPV2-c2 28 days apart. Infants (at 18–22 weeks of age) received 1 low dose or high dose of novel OPV2-c1 or novel OPV2-c2; randomly selected subsets (n = 50) of each group received a second dose 28 days later. Parents monitored and reported adverse events postvaccination. Type 2 poliovirus neutralizing antibodies were measured at days 0, 7, 28, and 56, and stool viral shedding was assessed up to 28 days postvaccination. The primary objective was the safety in all participants and noninferiority of the novel OPV2 day 28 seroprotection versus monovalent OPV2 in infants.In the novel OPV2 study, 47 children received the OPV2-c1 vaccine, and 53 received the OPV2-c2 vaccine as their first dose. A total of 97 of 100 children received a second dose; 45 children obtained the OPV2-c1 vaccine, and 52 received the novel OPV2-c2 vaccine. A total of 574 infants received the first dose of the novel OPV2 vaccine. A total of 36% of children (17 of 47) after the OPV2-c1vaccine and 26% of children (14 of 53) after the OPV2-c2 vaccine reported adverse events, consisting of loss of appetite, crying, fever, and irritability. There were 9 serious adverse events after OPV2-c1 and 13 after OPV2-c2 noted postvaccination (mostly pneumonia or bronchiolitis; 1 death from severe pneumonia), but none were believed to be causally associated with the vaccine. Infants also experienced crying, irritability, fever, and vomiting. The authors reported no consistent pattern of laboratory abnormalities or changes in laboratory assessments in both infants and children. Evaluable seroconversion rates were 94% to 100% after 1 to 2 doses in the novel OPV2 groups. The low-dose and high dose OPV2-c1 and the high dose OPV2-c2 met noninferiority criterion. Almost all infants who received either high dose OPV2-c1 or OPV2-c2 had shedding of type 2 virus in stools at day 7.The novel OPV 2 candidates appeared to be safe and immunogenic in children and infants in Panama. These candidates may represent a mechanism to decrease transmission of circulating neurovirulent type 2 vaccine-derived polioviruses.In the study, the authors report both results with the novel OPV2 vaccine candidates and a baseline study with monovalent Sabin OPV2 before cessation of administration. Most doses were administered to infants who experienced mostly transient and mild adverse effects. Noninferiority criterion was met with the high dose and low-dose OPV2-c1 and high dose OPV2-c2 vaccines. These novel candidates potentially represent a mechanism for immunity against type 2 polioviruses and the OPV2-c1 vaccine was listed under the World Health Organization Emergency Use for use against type 2 circulating vaccine-derived poliovirus outbreaks. With further larger studies, researchers will shed further light on safety, tolerability, and immunogenicity.