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发布于:2019-6-17 19:26:52  访问:25 次 回复:0 篇
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(HNS2) had a longterm nonprogressive HIV-1 infection for {more|much more
(HNS2) had a longterm nonprogressive HIV-1 infection for much more than 10 years.12 Relatively cross-reactive antibodies that neutralize primary isolates have already been described in sera from other donors with long-term nonprogressive HIV-1 infections.13 The EnvR2, expressed from on the list of env genes cloned from patient HNS2, could be neutralized by sera from individuals infected with HIV-1 from clades A, B, C, D, and F, at the same time as circulating recombinant forms (CRF).12 Virions pseudotyped with all the EnvR2 can mediate CD4independent infection. Additionally, these viruses are sensitive to neutralization by a panel of monoclonal antibodies that recognizes conformation epitopes in envelope.14 A uncommon mutation found within the crown of the V3 loop, a proline (P) and methionine (M) (nucleotide position 313/314), appears accountable for the uncommon neutralization sensitivity phenotype PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25272289 and also the capacity of this envelope to mediate CD4-independent infection.14 Recently, Dong et al.15 expressed the EnvR2 from a Venezuelan equine encephalitis (VEE) replicon and elicited higher titer neutralizing antibodies in mice and rabbits following immunization. These properties are consistent with all the possibility that the EnvR2 expresses a single or far more neutralization epitopes that happen to be responsible for induction of cross-reactive neutralizing antibodies in the donor of HNS2. DNA vaccination (genetic vaccination) induces protective immunity against various pathogens.16?9 These genetic vaccines consist of eukaryotic expression plasmids which might be inoculated into target cells inside the skin, muscle, or mucosal surfaces of a host and are translated into proteins.7,20 DNA vaccination successfully induces each humoral and cellular immune responses to immunogens PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/19502531 from diverse infectious agents.5,17?9,21?three The use of various HIV envelope immunogens has failed to induce antibodies capable of neutralizing extra than a fraction of primary isolates.five,7 In contrast to most immunogens, several DNA immunizations are needed to elicit even modest titers of neutralizing antibody to the HIV envelope glycoprotein.17,18,22,24?0 Nonetheless, the elicitation of neutralizing antibodies appears to become a critical SAR-260301cost element of any HIV vaccine.20,31 One strategy advanced in our laboratory to improve the immunogenicity to HIV-1 Env may be the use from the complement protein, C3d, as a molecular adjuvant. Conjugation of many copies of C3d to an antigen enhances the immunogenicity of low or nonimmunogenic antigens.27, 32 C3d, when fused to an antigen, but not when coinoculated, enhances the total IgG titer against the conjugated protein.27,32 Antibodies directed against (1) the hemagglutinin of influenza or measles virus,22,33,34 (2) the merozoite surface antigen, MSP1.19, of Plasmodium yoelii,35 (three) the capsular polysaccharide of serotype 14 Streptococcus pneumonia,36,37 (four) the hepatatis B surface antigen (L. Wang, individual communication) were improved among 1 and 3 logs following immunization with DNA-expressing C3d-conjugated antigens. The addition of 3 copies of murine or human C3d to soluble types of HIV-1 envelope accelerated both the onset as well as the avidity maturation of antibody in vaccinated mice and enhanced neutralizing antibody titers compared to mice vaccinated with antigen alone.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAIDS Res Hum Retroviruses.
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