A vault nanoparticle vaccine induces protective mucosal immunity.
BACKGROUND
Generation of robust cell-mediated immune responses at mucosal surfaces while reducing overall inflammation is a primary goal for vaccination. Here we report the use of a recombinant nanoparticle as a vaccine delivery platform against mucosal infections requiring T cell-mediated immunity for eradication.


RESULTS
We encapsulated an immunogenic protein, the major outer membrane protein (MOMP) of Chlamydia muridarum, within hollow, vault nanocapsules (MOMP-vaults) that were engineered to bind IgG for enhanced immunity. Intranasal immunization (i.n) with MOMP-vaults induced anti-chlamydial immunity plus significantly attenuated bacterial burden following challenge infection. Vault immunization induced anti-chlamydial immune responses and inflammasome formation but did not activate toll-like receptors. Moreover, MOMP-vault immunization enhanced microbial eradication without the inflammation usually associated with adjuvants.


CONCLUSIONS
Vault nanoparticles containing immunogenic proteins delivered to the respiratory tract by the i.n. route can act as "smart adjuvants" for inducing protective immunity at distant mucosal surfaces while avoiding destructive inflammation.
Champion
Cheryl I
CI
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America.
Kickhoefer
Valerie A
VA
Liu
Guangchao
G
Moniz
Raymond J
RJ
Freed
Amanda S
AS
Bergmann
Liisa L
LL
Vaccari
Dana
D
Raval-Fernandes
Sujna
S
Chan
Ann M
AM
Rome
Leonard H
LH
Kelly
Kathleen A
KA
D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000627:therapeutic use; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D023502:Chlamydia muridarum / Q000276:immunology; D004339:Drug Compounding / Q000379:methods; D018928:Immunity, Mucosal / Q000187:drug effects* / Q000276:immunology; D007249:Inflammation / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage*; D016896:Treatment Outcome
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines