RESUMO
The importance of natural IgM antibodies in protection against infections is still emerging and these antibodies have a potential role in the maintenance of homeostasis through clearance of apoptotic bodies, complement-dependent mechanisms, inflammation and exclusion of misfolded proteins. Natural IgM act as a first line of defence against unknown hazardous factors and are present in most vertebrates. We investigated the functional capacity of anti-HIV-1 IgM monoclonal antibodies, from a combinatorial Fab library derived from healthy individuals, and evaluated their protective role in inhibiting HIV-1 in vitro when passing across the human mucosal epithelial barrier. Primary HIV-1 isolates were efficiently transmitted over the tight polarized epithelial cells when added to their apical surface. Efficient inhibition of HIV-1 transmission was achieved when anti-HIV-1 IgM monoclonal antibodies were added to the basolateral side of the cells. Two of these human IgM MoAbs had the ability to neutralize HIV and reduced infection of dendritic cells in primary cervico-vaginal tissue biopsies in vitro. This indicates a potential role of natural IgM antibodies in the reduction of HIV-1 transmission in mucosal tissues and improve our understanding of how natural IgM antibodies against a neutralizing epitope could interfere with viral transmission.
Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Anti-HIV/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Imunoglobulina M/imunologia , Anticorpos Monoclonais/administração & dosagem , Biópsia , Células CACO-2 , Polaridade Celular/imunologia , Colo do Útero/citologia , Colo do Útero/imunologia , Colo do Útero/patologia , Colo do Útero/virologia , Células Dendríticas/imunologia , Células Dendríticas/virologia , Feminino , Anticorpos Anti-HIV/administração & dosagem , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/patologia , Infecções por HIV/transmissão , Voluntários Saudáveis , Humanos , Fragmentos Fab das Imunoglobulinas/sangue , Fragmentos Fab das Imunoglobulinas/imunologia , Imunoglobulina M/administração & dosagem , Mucosa/citologia , Mucosa/imunologia , Mucosa/virologia , Biblioteca de Peptídeos , Cultura Primária de Células , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Transcitose/imunologia , Vagina/citologia , Vagina/imunologia , Vagina/patologia , Vagina/virologiaRESUMO
AIMS: The study was designed to evaluate a novel cationic lipid DNA adjuvant (N3) and its function for HIV-1gp160/rev DNA plasmid delivered intranasally. The primary N3/HIV-DNA plasmid immunizations were boosted intranasally with a gp41 peptide in a anionic L3 adjuvant. This novel prime-boost strategy of mucosal immunization provided a broad HIV-1 envelope specific immunity, and recognition of viruses of subtypes A, B and C. CONCLUSIONS: Intranasal N3-adjuvanted gp160/rev DNA prime followed by one L3-peptide boosting immunization, induced broadly neutralizing antibodies against HIV-1 in the mucosa and systemically. The needle-free intranasal prime-boost strategy using two different adjuvant formulations reduced significantly the dose of DNA needed.