Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response

Joshua M. DiNapoli, Lijuan Yang, Siba K. Samal, Brian R. Murphy, Peter L. Collins, Alexander Bukreyev

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

We previously developed a respiratory tract vaccine candidate against Ebola virus (EBOV) based on human parainfluenza virus type 3 (HPIV3), a respiratory paramyxovirus, expressing the EBOV GP envelope protein (HPIV3/GP) from an added gene. Two doses of this vaccine candidate delivered by the intranasal and intratracheal route protected monkeys against intraperitoneal challenge with EBOV; however, concerns exist that the vaccine candidate may have reduced immunogenicity in the adult human population due to pre-existing immunity against HPIV3. Here we developed a new vaccine candidate (NDV/GP) based on Newcastle disease virus (NDV), an avian paramyxovirus that is antigenically distinct from human viral pathogens and is highly attenuated in monkeys. Following one intranasal and intratracheal inoculation of Rhesus monkeys with NDV/GP, titers of EBOV-specific antibodies in respiratory tract secretions and serum samples determined by ELISA, as well as serum EBOV-neutralizing antibodies, were undetectable or low compared to those induced by HPIV3/GP. A second immunization resulted in a substantial boost in serum IgG ELISA titers, yet the titers remained lower than those induced by a second dose of HPIV3/GP. In contrast, the ELISA IgA titers in respiratory tract secretions and, more importantly, the serum EBOV-neutralizing antibody titers were equal to those induced after the second dose of HPIV3/GP. These data suggest that NDV/GP can be effective for immunization against EBOV alone, or in combination with either HPIV3/GP or another vaccine platform in a heterologous prime-boost regimen.

Original languageEnglish (US)
Pages (from-to)17-25
Number of pages9
JournalVaccine
Volume29
Issue number1
DOIs
StatePublished - Dec 10 2010
Externally publishedYes

Fingerprint

Ebolavirus
Human parainfluenza virus 3
Newcastle disease virus
Neutralizing Antibodies
neutralizing antibodies
respiratory system
Respiratory System
Primates
Antibody Formation
Immunization
immunization
Vaccines
vaccines
viruses
enzyme-linked immunosorbent assay
monkeys
dosage
Rubulavirus
secretion
Respirovirus

Keywords

  • Antibody
  • Ebola virus
  • Immunization
  • Monkey
  • Newcastle disease virus
  • Respiratory tract
  • Vaccine
  • Vector

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response. / DiNapoli, Joshua M.; Yang, Lijuan; Samal, Siba K.; Murphy, Brian R.; Collins, Peter L.; Bukreyev, Alexander.

In: Vaccine, Vol. 29, No. 1, 10.12.2010, p. 17-25.

Research output: Contribution to journalArticle

DiNapoli, Joshua M. ; Yang, Lijuan ; Samal, Siba K. ; Murphy, Brian R. ; Collins, Peter L. ; Bukreyev, Alexander. / Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response. In: Vaccine. 2010 ; Vol. 29, No. 1. pp. 17-25.
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