Intradermal immunization improves protective efficacy of a novel TB vaccine candidate.
We have developed the Mycobacterium tuberculosis (Mtb) fusion protein (ID83), which contains the three Mtb proteins Rv1813, Rv3620 and Rv2608. We evaluated the immunogenicity and protective efficacy of ID83 in combination with several emulsion-formulated toll-like receptor agonists. The ID83 subunit vaccines containing synthetic TLR4 or TLR9 agonists generated a T helper-1 immune response and protected mice against challenge with Mtb regardless of route. The ID83 vaccine formulated with gardiquimod (a TLR7 agonist) also resulted in a protective response when administered intradermally, whereas the same vaccine given subcutaneously failed to provide protection. This highlights the need to explore different routes of immunization based on the adjuvant formulations used.
Baldwin
Susan L
SL
Infectious Disease Research Institute, Seattle, WA 98104, USA. sbaldwin@idri.org
Bertholet
Sylvie
S
Kahn
Maria
M
Zharkikh
Irina
I
Ireton
Gregory C
GC
Vedvick
Thomas S
TS
Reed
Steven G
SG
Coler
Rhea N
RN
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists; D051199:Toll-Like Receptor 7 / Q000819:agonists; D051217:Toll-Like Receptor 9 / Q000819:agonists; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; D014764:Viral Proteins