RESUMO
Neuraminidase is suggested as an important component for developing a universal influenza vaccine. Targeted induction of neuraminidase-specific broadly protective antibodies by vaccinations is challenging. To overcome this, we rationally select the highly conserved peptides from the consensus amino acid sequence of the globular head domains of neuraminidase. Inspired by the B cell receptor evolution process, a reliable sequential immunization regimen is designed to result in immuno-focusing by steering bulk immune responses to a selected region where broadly protective B lymphocyte epitopes reside. After priming neuraminidase protein-specific antibody responses in C57BL/6 or BALB/c inbred mice strains by immunization or pre-infection, boost immunizations with certain neuraminidase-derived peptide-keyhole limpet hemocyanin conjugates significantly strengthened serum neuraminidase inhibition activities and cross-protections. Overall, this study provides proof of concept for a peptide-based sequential immunization strategy for achieving targeted induction of cross-protective antibody response, which provides references for designing universal vaccines against other highly variable pathogens.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Virus da Influenza A Subtipo H5N1 , Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Animais , Camundongos , Humanos , Infecções por Orthomyxoviridae/prevenção & controle , Neuraminidase , Anticorpos Antivirais , Camundongos Endogâmicos C57BL , Vacinação , Peptídeos , Camundongos Endogâmicos BALB C , Glicoproteínas de Hemaglutininação de Vírus da InfluenzaRESUMO
Astroviruses (AstVs) have a very wide range of hosts and are associated with enteric and extra-enteric disease in mammals and birds. Cross-species transmission of AstVs has been observed frequently. In the present study, the genome of a novel astrovirus from Amur tigers (Panthera tigris) from a zoo in China was characterized and was found to have the typical genomic features of other mammal AstVs. It showed the highest nucleotide sequence similarity (46.1-87.3% identity) to AstVs from cats, indicating a close phylogenetic relationship and possible cross-species transmission between them. To our knowledge, this is the first identification and characterization of AstV from tigers, and this virus is the third astrovirus identified in hosts of the family Felidae. The results of this study will be helpful for understanding the origin, genetic diversity, and cross-species transmission of AstV.
