Combinatorial Viral Vector-Based and Live Attenuated Vaccines without an Adjuvant to Generate Broader Immune Responses to Effectively Combat Pneumonic Plague

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7 Scopus citations

Abstract

Mice immunized with a combination of an adenovirus vector (Ad5-YFV) and live-attenuated (LMA)-based vaccines were evaluated for protective efficacy against pneumonic plague. While the Ad5-YFV vaccine harbors a fusion cassette of three genes encoding YscF, F1, and LcrV, LMA represents a mutant of parental Yersinia pestis CO92 deleted for genes encoding Lpp, MsbB, and Ail. Ad5-YFV and LMA were either administered simultaneously (1-dose regimen) or 21 days apart in various orders and route of administration combinations (2-dose regimen). The 2- dose regimen induced robust immune responses to provide full protection to animals against parental CO92 and its isogenic F1 deletion mutant (CAF2) challenges during both short- and long-term studies. Mice intranasally (i.n.) immunized with Ad5-YFV first followed by LMA (i.n. or intramuscularly [i.m.]) had higher T- and B-cell proliferative responses and LcrV antibody titers than those in mice vaccinated with LMA (i.n. or i.m.) first ahead of Ad5-YFV (i.n.) during the long-term study. Specifically, the needle- and adjuvant-free vaccine combination (i.n.) is ideal for use in plague regions of endemicity. Conversely, with a 1-dose regimen, mice vaccinated with Ad5-YFV i.n. and LMA by the i.m. route provided complete protection to animals against CO92 and its CAF2 mutant challenges and elicited Th1/Th2, as well as Th17 responses, making it suitable for emergency vaccination during a plague outbreak or bioterrorist attack. This is a first study in which a viral vector-based and live-attenuated vaccines were effectively used in combination, representing adjuvant- and/or needle-free immunization, with each vaccine triggering a distinct cellular immune response.

Original languageEnglish (US)
Article numbere03223-21
JournalmBio
Volume12
Issue number6
DOIs
StatePublished - Dec 1 2021

Keywords

  • Capsular antigen F1-minus mutant
  • Cell-mediated immune responses
  • Heterologous prime-boost or simultaneous immunization
  • Humoral
  • Mucosal
  • Pneumonic plague mouse model
  • Rag1 knockout mice
  • Yersinia pestis CO92

ASJC Scopus subject areas

  • Microbiology
  • Virology

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