Intranasal vaccination with adjuvant-free S. aureus antigens effectively protects mice against experimental sepsis.
Staphylococcus aureus (S. aureus) is a Gram-positive coccal bacterium comprising part of the human skin, nares and gastrointestinal tract normal microbiota. It is also an important cause of nosocomial/community-acquired infections in humans and animals, which can cause a diverse array of infections, including sepsis, which is a progressive systemic inflammation response syndrome that is frequently fatal. The emergence of drug-resistant strains and the high toxicity of the treatments used for these infections point out the need to develop an effective, inexpensive and safe vaccine that can be used prophylactically. In this work, we used an experimental sepsis model to evaluate the effectiveness of whole antigens from S. aureus (SaAg) given by the intranasal route to induce protective immunity against S. aureus infection in mice. BALB/c mice were vaccinated via intranasal or intramuscular route with two doses of SaAg, followed by biocompatibility and immunogenicity evaluations. Vaccinated animals did not show any adverse effects associated with the vaccine, as determined by transaminase and creatinine measurements. Intranasal, but not intramuscular vaccination with SaAg led to a significant reduction in IL-10 production and was associated with increased level of IFN-γ and NO. SaAg intranasal vaccination was able to prime cellular and humoral immune responses and inducing a higher proliferation index and increased production of specific IgG1/IgG2, which contributed to decrease the bacterial load in both liver and the spleen and improve survival during sepsis. These findings present the first evidence of the effectiveness of whole Ag intranasal-based vaccine administration, which expands the vaccination possibilities against S. aureus infection.
Núcleo de Biotecnologia, Universidade Federal do Espírito Santo - UFES, Vitória, Brazil.
Nataly Pescinalli
NP
Stegmiller
Núcleo de Biotecnologia, Universidade Federal do Espírito Santo - UFES, Vitória, Brazil.
Estevão Carlos
EC
Barcelos
Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo - UFES, Vitória, Brazil.
Janine Miranda
JM
Leal
Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo - UFES, Vitória, Brazil.
Luciana Polaco
LP
Covre
Departamento de Medicina Veterinária, Universidade Federal do Espírito Santo - UFES, Alegre, Brazil.
Dirlei Molinari
DM
Donatele
Instituto de Biofísica Carlos Chagas Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Herbet Leonel
HL
de Matos Guedes
Núcleo de Biotecnologia, Universidade Federal do Espírito Santo - UFES, Vitória, Brazil.
Marco Cesar
MC
Cunegundes
Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo - UFES, Vitória, Brazil.
Rodrigo Ribeiro
RR
Rodrigues
Núcleo de Biotecnologia, Universidade Federal do Espírito Santo - UFES, Vitória, Brazil; Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo - UFES, Vitória, Brazil. Electronic address: dgomes@ndi.ufes.br.
Daniel Cláudio Oliviera
DC
Gomes
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D058491:Bacterial Load; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008099:Liver / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D018805:Sepsis / Q000517:prevention & control*; D013154:Spleen / Q000276:immunology; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D013209:Staphylococcal Vaccines; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma
Intranasal vaccination; Sepsis; Staphylococcus aureus