Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic

Abstract

Each year, approximately five million people die worldwide from putatively vaccine-preventable mucosally transmitted diseases. With respect to mass vaccination campaigns, one strategy to cope with this formidable challenge is aerosol vaccine delivery, which offers potential safety, logistical, and cost-saving advantages over traditional vaccination routes. Additionally, aerosol vaccination may elicit pivotal mucosal immune responses that could contain or eliminate mucosally transmitted pathogens in a preventative or therapeutic vaccine context. In this current preclinical non-human primate investigation, we demonstrate the feasibility of aerosol vaccination with the recombinant poxvirus-based vaccine vectors NYVAC and MVA. Real-time in vivo scintigraphy experiments with radiolabeled, aerosol-administered NYVAC-C (Clade C, HIV-1 vaccine) and MVA-HPV vaccines revealed consistent mucosal delivery to the respiratory tract. Furthermore, aerosol delivery of the vaccines was safe, inducing no vaccine-associated pathology, in particular in the brain and lungs, and was immunogenic. Administration of a DNA-C/NYVAC-C prime/boost regime resulted in both systemic and anal-genital HIV-specific immune responses that were still detectable 5 months after immunization. Thus, aerosol vaccination with NYVAC and MVA vectored vaccines constitutes a tool for large-scale vaccine efforts against mucosally transmitted pathogens.MVA HPV ͉ non-human primate ͉ NYVAC HIV ͉ preclinical study ͉ aerosol vaccine assessment

Newcastle Disease Virus-Vectored Vaccines Expressing the Hemagglutinin or Neuraminidase Protein of H5N1 Highly Pathogenic Avian Influenza Virus Protect against Virus Challenge in Monkeys

“…It is generally accepted that particles less than 3 m in diameter readily penetrate the small airways (reviewed in reference 45). Since the typical efficiency of delivery of aerosol particles to the lower respiratory tract in primate models is approximately 10% (13,16), we used a 20-fold-higher dose (4 ϫ 10 8 PFU) for administration by nebulizer. NS samples taken on days 2, 4, 6, and 8 after the first vaccine dose demonstrated a lack of any significant NDV shedding from the upper respiratory tract in all groups except the NDV/HA (aerosol) group, in which modest shedding (Յ2 log 10 PFU/ml) was detected.…”

Preclinical Studies of a Modified Vaccinia Virus Ankara-Based HIV Candidate Vaccine: Antigen Presentation and Antiviral Effect

“…Traditional application routes include intramuscular and subcutaneous immunization, and alternative strategies targeting mucosal immunity are currently being developed (8,30). We screened a panel of human primary and immortalized cells of various origins for susceptibility to MVA.…”

Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses

“…delivery at 10 7.3 PFU per site in the form of a liquid. While aerosol particles less than 3 μM in diameter readily penetrate the small airways (26), the recipients of aerosolized HPIV3/EboGP received a 10-fold higher dose of the vaccine to account for a 10% delivery efficiency of aerosol particles to the lower respiratory tract in primate models due to small lung size and shallow breathing patterns (27,28) further exacerbated by anesthesia during vaccination (26). The VRP group was vaccinated by 2 sequential s.c. injections of 10 10 infecinto the vector particle and was functional in mediating infection of the respiratory tract, but did not alter the tropism of the vaccine virus (18)(19)(20).…”