Recombinant Salmonella enterica serovar Typhi in a prime-boost strategy.
This study investigated the utility of attenuated Salmonella enterica serovar Typhi strain CVD 908-htrA (908 h) in a heterologous prime-boost strategy. Mice primed intranasally (i.n.) with 908 h expressing fragment C (Frag C) of tetanus toxin and boosted intramuscularly (i.m.) with tetanus toxoid (TT) mounted enhanced and accelerated serum IgG anti-Frag C responses in comparison to unprimed, vector-primed and homologously-primed and boosted mice. Serum antitoxin responses were also determined; mice that were vaccinated following a heterologous prime-boost regimen exhibited the highest levels of Frag C-specific toxin neutralizing antibodies 1 week after boosting. Mice primed and boosted i.m. with TT developed a significantly greater proportion of serum IgG1 antibodies and weaker IFN-gamma levels in contrast to those primed intranasally (i.n.) with rS. Typhi that were homologously or heterologously boosted. These encouraging pre-clinical data provide a rational basis for undertaking a pilot clinical trial to evaluate this strategy. An ability to stimulate enhanced, accelerated responses to parenteral vaccination following mucosal priming may be advantageous in the immunoprophylaxis of many infectious diseases, including those of biodefense importance.
Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA.
Christofer J
CJ
Vindurampulle
Lilian F
LF
Cuberos
Eileen M
EM
Barry
Marcela F
MF
Pasetti
Myron M
MM
Levine
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis; D000917:Antibody Formation / Q000276:immunology; D002452:Cell Count; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019779:Salmonella enterica / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013744:Tetanus Toxin / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D022562:Salmonella Vaccines; D013744:Tetanus Toxin; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic; D007371:Interferon-gamma