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1.
Hum Vaccin ; 3(4): 109-15, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17611417

RESUMO

Human papillomavirus (HPV) types 6, 11, 16 and 18 L1 virus-like particles (VLPs) have been used to generate the prophylactic quadrivalent vaccine, Gardasil. There is a high degree of L1 homology between HPV types and it is likely that there is a substantial degree of surface exposed viral epitope similarity. An investigation of vaccine-induced antibody binding and neutralization was undertaken focusing on A7 species members, HPV 18 and 45. Polyclonal sera from Gardasil recipients and from HPV 18 L1 VLP recipients were evaluated. Vaccine-induced antibodies were found to cross-neutralize HPV 45 pseudovirions (PsV) in vitro. Examination of a panel of monoclonal antibodies made against L1 VLPs revealed the presence of conformational, neutralizing epitopes on the surface of VLPs that may be shared between HPV 18 and HPV 45. These data demonstrate that Gardasil(r) immunization induces antibodies capable of neutralizing HPV 18 PsV and HPV 45 PsV in vitro.


Assuntos
Anticorpos Antivirais/imunologia , Proteínas do Capsídeo/imunologia , Papillomaviridae/imunologia , Vacinas contra Papillomavirus/imunologia , Vírion/imunologia , Adolescente , Adulto , Anticorpos Monoclonais/imunologia , Formação de Anticorpos , Reações Cruzadas , Feminino , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Papillomavirus Humano 18/imunologia , Humanos , Imunização , Infecções por Papillomavirus/prevenção & controle
2.
Infect Immun ; 74(4): 2215-23, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16552052

RESUMO

Staphylococcus aureus is a major cause of nosocomial infections worldwide, and the rate of resistance to clinically relevant antibiotics, such as methicillin, is increasing; furthermore, there has been an increase in the number of methicillin-resistant S. aureus community-acquired infections. Effective treatment and prevention strategies are urgently needed. We investigated the potential of the S. aureus surface protein iron surface determinant B (IsdB) as a prophylactic vaccine against S. aureus infection. IsdB is an iron-sequestering protein that is conserved in diverse S. aureus clinical isolates, both methicillin resistant and methicillin sensitive, and it is expressed on the surface of all isolates tested. The vaccine was highly immunogenic in mice when it was formulated with amorphous aluminum hydroxyphosphate sulfate adjuvant, and the resulting antibody responses were associated with reproducible and significant protection in animal models of infection. The specificity of the protective immune responses in mice was demonstrated by using an S. aureus strain deficient for IsdB and HarA, a protein with a high level of identity to IsdB. We also demonstrated that IsdB is highly immunogenic in rhesus macaques, inducing a more-than-fivefold increase in antibody titers after a single immunization. Based on the data presented here, IsdB has excellent prospects for use as a vaccine against S. aureus disease in humans.


Assuntos
Anticorpos Antibacterianos/biossíntese , Antígenos de Bactérias/imunologia , Proteínas de Transporte de Cátions/imunologia , Macaca mulatta/imunologia , Sepse/imunologia , Infecções Estafilocócicas/imunologia , Vacinas Antiestafilocócicas/imunologia , Staphylococcus aureus/imunologia , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/química , Proteínas de Transporte de Cátions/administração & dosagem , Proteínas de Transporte de Cátions/química , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Sepse/mortalidade , Sepse/prevenção & controle , Homologia de Sequência de Aminoácidos , Infecções Estafilocócicas/mortalidade , Infecções Estafilocócicas/prevenção & controle , Vacinas Antiestafilocócicas/administração & dosagem , Staphylococcus aureus/isolamento & purificação , Taxa de Sobrevida
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