A bacteriophage T4 nanoparticle-based dual vaccine against anthrax and plague

Pan Tao, Marthandan Mahalingam, Jingen Zhu, Mahtab Moayeri, Jian Sha, William Lawrence, Stephen H. Leppla, Ashok Chopra, Venigalla B. Rao

Research output: Contribution to journalArticle

Abstract

Bacillus anthracis and Yersinia pestis, the causative agents of anthrax and plague, respectively, are two of the deadliest pathogenic bacteria that have been used as biological warfare agents. Although Biothrax is a licensed vaccine against anthrax, no Food and Drug Administration-approved vaccine exists for plague. Here, we report the development of a dual anthrax-plague nanoparticle vaccine employing bacteriophage (phage) T4 as a platform. Using an in vitro assembly system, the 120-by 86-nm heads (capsids) of phage T4 were arrayed with anthrax and plague antigens fused to the small outer capsid protein Soc (9 kDa). The antigens included the anthrax protective antigen (PA) (83 kDa) and the mutated (mut) capsular antigen F1 and the low-calcium-response V antigen of the type 3 secretion system from Y. pestis (F1mutV) (56 kDa). These viral nanoparticles elicited robust anthrax-and plague-specific immune responses and provided complete protection against inhalational anthrax and/or pneumonic plague in three animal challenge models, namely, mice, rats, and rabbits. Protection was demonstrated even when the animals were simultaneously challenged with lethal doses of both anthrax lethal toxin and Y. pestis CO92 bacteria. Unlike the traditional subunit vaccines, the phage T4 vaccine uses a highly stable nanoparticle scaffold, provides multivalency, requires no adjuvant, and elicits broad T-helper 1 and 2 immune responses that are essential for complete clearance of bacteria during infection. Therefore, phage T4 is a unique nanoparticle platform to formulate multivalent vaccines against high-risk pathogens for national preparedness against potential bioterror attacks and emerging infections. IMPORTANCE Following the deadly anthrax attacks of 2001, the Centers for Disease Control and Prevention (CDC) determined that Bacillus anthracis and Yersinia pestis that cause anthrax and plague, respectively, are two Tier 1 select agents that pose the greatest threat to the national security of the United States. Both cause rapid death, in 3 to 6 days, of exposed individuals. We engineered a virus nanoparticle vaccine using bacteriophage T4 by incorporating key antigens of both B. anthracis and Y. pestis into one formulation. Two doses of this vaccine provided complete protection against both inhalational anthrax and pneumonic plague in animal models. This dual anthrax-plague vaccine is a strong candidate for stockpiling against a potential bioterror attack involving either one or both of these biothreat agents. Further, our results establish the T4 nanoparticle as a novel platform to develop multivalent vaccines against pathogens of high public health significance.

LanguageEnglish (US)
Article numbere01926-18
JournalmBio
Volume9
Issue number5
DOIs
StatePublished - Sep 1 2018

Fingerprint

Plague Vaccine
Anthrax Vaccines
Anthrax
Bacteriophage T4
Nanoparticles
Plague
Yersinia pestis
Vaccines
Bacillus anthracis
Antigens
Bacteria
Animal Models
Biological Warfare Agents
Security Measures
Subunit Vaccines
Capsid
Capsid Proteins
United States Food and Drug Administration
Centers for Disease Control and Prevention (U.S.)
Infection

Keywords

  • Anthrax vaccine
  • Bacteriophage T4
  • Biodefense
  • Plague vaccine
  • Small outer capsid protein
  • Vaccine delivery
  • Virus nanoparticles

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

A bacteriophage T4 nanoparticle-based dual vaccine against anthrax and plague. / Tao, Pan; Mahalingam, Marthandan; Zhu, Jingen; Moayeri, Mahtab; Sha, Jian; Lawrence, William; Leppla, Stephen H.; Chopra, Ashok; Rao, Venigalla B.

In: mBio, Vol. 9, No. 5, e01926-18, 01.09.2018.

Research output: Contribution to journalArticle

Tao, P, Mahalingam, M, Zhu, J, Moayeri, M, Sha, J, Lawrence, W, Leppla, SH, Chopra, A & Rao, VB 2018, 'A bacteriophage T4 nanoparticle-based dual vaccine against anthrax and plague' mBio, vol. 9, no. 5, e01926-18. https://doi.org/10.1128/mBio.01926-18
Tao, Pan ; Mahalingam, Marthandan ; Zhu, Jingen ; Moayeri, Mahtab ; Sha, Jian ; Lawrence, William ; Leppla, Stephen H. ; Chopra, Ashok ; Rao, Venigalla B. / A bacteriophage T4 nanoparticle-based dual vaccine against anthrax and plague. In: mBio. 2018 ; Vol. 9, No. 5.
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