Safety and Immunogenicity of an Intranasal Sendai Virus-Based Human Parainfluenza Virus Type 1 Vaccine in 3- to 6-Year-Old Children

Abstract

, or 5 ؋ 10 7 50% egg infectious doses) was delivered by the intranasal route to each study participant. The vaccine was well tolerated by all the study participants. There was no sign of vaccine virus replication in the airway in any participant. Most children exhibited an increase in antibody binding and neutralizing responses toward hPIV-1 within 4 weeks from the time of vaccination. In several children, antibody responses remained above incoming levels for at least 6 months after vaccination. Data suggest that SeV may provide a benefit to 3-to 6-year-old children, even when vaccine recipients have preexisting cross-reactive antibodies due to previous exposures to hPIV-1. Results encourage the testing of SeV administration in young seronegative children to protect against the serious respiratory tract diseases caused by hPIV-1 infections. Human parainfluenza virus type 1 (hPIV-1) is a member of the Paramyxoviridae family. It is the major cause of laryngotracheobronchitis (croup) and can also mediate bronchiolitis and pneumonia, most commonly in children (1, 2). There have been previous attempts to develop a vaccine against hPIV-1, but no vaccine has yet been licensed (3,4). A study of a formalin-treated hPIV-1 vaccine in the 1960s demonstrated safety but not efficacy (5).We have pursued the development of a Jennerian (xenotropic) vaccine approach. Our previous studies showed that Sendai virus (SeV), a murine PIV, had both sequence and antigenic similarity with hPIV-1 (6-9). We found that hPIV-1 protected mice from SeV infections and that SeV safely protected nonhuman primates from hPIV-1 infections (10, 11). SeV has also proven successful as a recombinant vaccine for other paramyxovirus pathogens in animal models (12-18).Historically, SeV has never caused disease in humans. Upon the first discovery of the virus in 1952, there was some concern that SeV was an etiological agent for human respiratory infections, but it was later determined that SeV is a pathogen of mice, not of humans (2,19,20). Moreover, when we tested SeV in a dose escalation phase I clinical study in human adult volunteers, we found that it was well tolerated and enhanced hPIV-1-specific antibody responses in some individuals (21). As a follow-up to the adult study, we tested SeV in a dose escalation study in 3-to 6-year-old PIV-1-seropositive children, and we describe here the early safety, tolerability, and immunogenicity data in this age group. MATERIALS AND METHODS Participants.Ten healthy children between the ages of 3 and 6 years (six males, four females) were vaccinated in a phase I dose escalation study of the SeV vaccine. The protocol was reviewed and approved by the U.S.Food and Drug Administration (FDA) and the St. Jude Children's Research Hospital Institutional Review Board. The study was performed only after data from a phase I study with SeV in adults were reviewed and approved by a data safety monitoring board.Vaccine. The vaccine was an unmodified live SeV (Enders strain) propagated in chick egg (Spafas, Inc., Preston, CT) all...

A Sendai virus recombinant vaccine expressing a gene for truncated human metapneumovirus (hMPV) fusion protein protects cotton rats from hMPV challenge

“…We have previously shown that SeV induces rapid and durable B and T cell responses systemically and in upper respiratory tract (URT) and lower respiratory tract (LRT) tissues [36, 37]. Non-recombinant SeV is currently in clinical trials and has been shown to be well tolerated in adults and 3–6 year old children [9, 11]. Tests in 1–2 year old children are ongoing.…”

“…The unmanipulated virus has already been tested in clinical trials in adults and children as a vaccine for hPIV-1, and has been shown to be well-tolerated and immunogenic. A recombinant SeV carrying HIV genes was also tested clinically, and a recombinant SeV vaccine for respiratory syncytial virus (RSV) is advancing toward clinical trials [9–14]. Here, we describe the production and testing of a recombinant SeV, named SeV-MPV-Ft that was produced by reverse genetics and carries a gene for a truncated hMPV fusion (F) protein.…”

First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus–Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens

“…SeV has been safely tested as a nonrecombinant Jennerian vaccine against hPIV-1 in adult and pediatric populations [22, 23]. Both SeV-vectored and Ad35-vectored vaccines were well tolerated, and adverse events were not significantly different from those in placebo recipients.…”

“…SeV is genetically and antigenically related to hPIV-1 [18–21]. A live nonrecombinant SeV vaccine against human parainfluenza virus type 1 (hPIV-1) administered intranasally in adults and young children was safe and immunogenic [22, 23]. SeV antibodies cross-reactive with hPIV-1 antibodies are present in most people [24].…”

T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders

“…In murine studies, SeV could elicit rapid and durable respiratory mucosa and systemic HPIV-specific B cell and T cell responses (Sealy et al, 2010;Rudraraju et al, 2011). Clinical testing of human populations infected with RSV and HPIVs is underway (Adderson et al, 2015). For a full review of current development of antiviral compounds and vaccine candidates tested against RSV, see Costello et al, 2012.…”