Intranasal vaccination with recombinant P6 protein and adamantylamide dipeptide as mucosal adjuvant confers efficient protection against otitis media and lung infection by nontypeable Haemophilus influenzae.
Nontypeable Haemophilus influenzae (NTHi) is a leading etiologic agent of otitis media in children and recurrent respiratory infections in patients with chronic obstructive pulmonary disease. The highly conserved outer membrane protein P6 constitutes a promising vaccine candidate antigen. However, the small amount of P6 produced by this fastidious microorganism renders large-scale production difficult. Controversial data also exist concerning the suitability of recombinant P6 (rP6) as a vaccine antigen. Therefore, we performed a comparative evaluation of the immunogenicity and efficacy of native P6 and rP6 in mice intranasally vaccinated with adamantylamide dipeptide (AdDP) as an adjuvant. High titers of P6-specific serum antibodies were elicited in mice vaccinated with either native P6 or rP6, which cross-recognized both antigens. However, rP6 stimulated stronger mucosal responses. Mice vaccinated with rP6 were protected against both pulmonary and middle-ear infections (P<.01). This demonstrates that rP6 plus AdDP constitutes a promising vaccine formulation against the most relevant forms of disease caused by NTHi.
Bertot
Gustavo M
GM
Virology Laboratory, Ricardo Gutierrez Children Hospital, Buenos Aires, Argentina. gmbertot@yahoo.com.ar.
Becker
Pablo D
PD
Guzmán
Carlos A
CA
Grinstein
Saúl
S
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000547:Amantadine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D004151:Dipeptides / Q000008:administration & dosage*; D005260:Female; D006192:Haemophilus Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006193:Haemophilus influenzae / Q000276:immunology*; D007114:Immunization / Q000379:methods; D008171:Lung Diseases / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010033:Otitis Media / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000276:immunology; D012463:Saliva / Q000382:microbiology; D014621:Vagina / Q000382:microbiology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D004151:Dipeptides; D018073:Haemophilus Vaccines; C069990:P6 outer membrane protein, Haemophilus; D011994:Recombinant Proteins; C044891:adamantylamide-alanyl-isoglutamine; D000547:Amantadine