The subgenus-specific C-terminal region of protein IX is located on the surface of the adenovirus capsid.
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We have investigated the antigenicity of the C- and N-terminal halves of pIX of human adenovirus types 2 and 3 (Ad2 and Ad3) as well as their orientations in virions. We found that only the C-terminal halves of Ad2 pIX and Ad3 pIX reacted in a subgenus-specific manner by enzyme-linked immunosorbent assay and immunoblot analysis. Based on immunoelectron microscopy experiments, pIX in viral capsids appears to be positioned such that the C-terminal part of pIX constitutes the surface domain whereas the N terminus of the protein makes up the internal domain in icosahedral Ad capsids. (+info)
Common neutralization epitope in minor capsid protein L2 of human papillomavirus types 16 and 6.
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Studies of virus neutralization by antibody are a prerequisite for development of a prophylactic vaccine strategy against human papillomaviruses (HPVs). Using HPV16 and -6 pseudovirions capable of inducing beta-galactosidase in infected monkey COS-1 cells, we examined the neutralizing activity of mouse monoclonal antibodies (MAbs) that recognize surface epitopes in HPV16 minor capsid protein L2. Two MAbs binding to a synthetic peptide with the HPV16 L2 sequence of amino acids (aa) 108 to 120 were found to inhibit pseudoinfections with HPV16 as well as HPV6. Antisera raised by immunizing BALB/c mice with the synthetic peptide had a cross-neutralizing activity similar to that of the MAb. The data indicate that HPV16 and -6 have a common cross-neutralization epitope (located within aa 108 to 120 of L2 in HPV16), suggesting that this epitope may be shared by other genital HPVs. (+info)
The role of gamma interferon in immune resistance to vaginal infection by herpes simplex virus type 2 in mice.
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We investigated the role of interferon gamma (IFN-gamma) in a mouse model of immunity to vaginal infection by herpes simplex virus type 2 (HSV-2). Within 8 h after immune mice were challenged intravaginally with HSV-2, IFN-gamma concentrations in vaginal secretions reached levels that can be antiviral in vitro. This rapid synthesis of IFN-gamma occurred in immune-challenged mice but not in nonimmune-challenged mice, indicating that it required memory T cells. Immunostaining and in situ hybridization revealed that the IFN-gamma was synthesized by cells whose morphological appearance suggested that they were lymphocytes and macrophage-like cells in the mucosa. The presence of IFN-gamma in vaginal secretions was correlated with upregulation of MHC class II antigens in the epithelium and with vigorous (30-fold) recruitment of T and B lymphocytes into the vagina. In vivo administration of anti-IFN-gamma to immune mice 17 h before virus challenge blocked the subsequent appearance of IFN-gamma in vaginal secretions, blocked upregulation of class II antigens, blocked adherence of T cells to endothelium and their recruitment into the vagina, and markedly reduced immunity against reinfection of the vaginal epithelium. (+info)
Neutralizing antibody responses and evolution of antigenic variants in monozygotic twin lambs infected with phenotypically distinct ovine lentiviruses.
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Ovine lentivirus (OvLV) isolates 85/34 (OvLV 34) and 84/28 (OvLV 28) were initially characterized as phenotypically distinct "rapid/high" and "slow/low" strains based on replication kinetics, syncytiogenesis, and cell lysis in vitro. In the present study, sera from OvLV-34- or OvLV-28-infected monozygotic twin lambs defined these virus strains as distinct neutralization serotypes. We also show that immune recognition of at least one OvLV neutralization epitope is influenced by genetic differences between lambs. Additional studies determined the neutralization phenotype of virus isolates from alveolar macrophages of OvLV-34- or OvLV-28-infected lambs, evaluated the role of neutralizing antibodies in selection and persistence of antigenic variants, and related the severity of OvLV-induced lymphoid interstitial pneumonia (LIP) to the evolution of neutralization variants. These studies demonstrate that (i) macrophage-associated OvLV neutralization variants can arise in the presence or the absence of neutralizing antibodies directed to inoculum viruses, (ii) OvLV variants persist in macrophages in the presence of serum neutralizing antibodies, and (iii) the emergence of OvLV variants is apparently unrelated to the severity of LIP. (+info)
Experimental inoculation of heifers with bovine adenovirus type 3.
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Nine 2-year-old heifers having BAd3-neutralizing antibody titers between 1:120 and 1:1080 were individually exposed intranasally to an aerosol of 10(8) pfu of wild type (wt) bovine adenovirus type 3 (BAd3). Four animals were kept as non-inoculated controls. The heifers were examined daily for rectal temperature, weight gain/loss, nasal and ocular discharges, and other clinical signs for 10 d post-inoculation. None of the animals showed any sign of clinical disease. Virus excretion was observed in one animal only on Day 3 post-inoculation. All BAd3-inoculated heifers demonstrated a significant (P < 0.005, paired t-test) rise in BAd3-specific serum IgG, IgG1, or IgG2 ELISA titers and virus-neutralizing antibody titers compared to the titers before inoculation. All virus-inoculated animals demonstrated increased levels of BAd3-specific IgA ELISA titers in nasal secretions. These results suggest that in the presence of circulating BAd3-neutralizing antibodies, intranasal inoculation of cattle with wt BAd3 would result in inapparent infection. (+info)
Synergistic effect of immunization with a peptide cocktail inducing antibody, helper and cytotoxic T-cell responses on protection against respiratory syncytial virus.
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Respiratory syncytial virus (RSV)-specific cytotoxic T lymphocytes (CTL) or neutralizing antibodies can protect against RSV infection when induced separately by immunization with synthetic peptides. In the work described here, RSV-specific neutralizing antibodies and CTLs were induced after immunization with a cocktail of peptides consisting of a B-cell mimotope (S1S-MAP), a T-helper epitope (SH:45-60) and a CTL epitope linked to a fusion (F) peptide (F/M2:81-95) that were comparable to those induced by the peptides alone. Following challenge, a 190-fold reduction in RSV titre was observed in the lungs of peptide cocktail-immunized mice. The combination of RSV-specific humoral and cellular immunity induced by the peptide cocktail was thus more effective at clearing RSV than peptide-induced humoral or cellular immunity alone. (+info)
Serum and intestinal isotype antibody responses to Wa human rotavirus in gnotobiotic pigs are modulated by maternal antibodies.
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The effects of passive antibodies on protection and active immune responses to human rotavirus were studied in gnotobiotic pigs. Pigs were injected at birth with saline or sow serum of high (immunized) or low (control) antibody titre and subsets of pigs were fed colostrum and milk from immunized or control sows. Pigs were inoculated at 3-5 days of age and challenged at 21 days post-inoculation (p.i.) with virulent Wa human rotavirus. Pigs receiving immune serum with or without immune colostrum/milk were partially protected against diarrhoea and virus shedding after inoculation, but had significantly lower IgA antibody titres in serum and small intestinal contents at 21 days p.i. and lower protection rates after challenge compared with pigs given control or no maternal antibodies. IgG antibody titres were consistently higher in small than in large intestinal contents. Pigs given control serum with control colostrum/milk had lower rates of virus shedding after inoculation than those given control serum alone. In summary, high titres of circulating maternal antibodies with or without local (milk) antibodies provided passive protection after inoculation but suppressed active mucosal antibody responses. These findings may have implications for the use of live, oral rotavirus vaccines in breast-fed infants. (+info)
In vivo activity of a mixture of two human monoclonal antibodies (anti-HBs) in a chronic hepatitis B virus carrier chimpanzee.
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A 35-year-old female hepatitis B virus carrier chimpanzee was infused with one dose of a mixture of human monoclonal antibodies 9H9 and 4-7B (antibodies against hepatitis B virus surface antigen; HBsAg). Blood samples were taken before and up to 3 weeks after infusion. HBsAg and antibodies against HBsAg (anti-HBs) were quantified by radioimmunoassay and enzyme immunoassay. Free anti-HBs was never detected. Thirty min after the start of the infusion the HBsAg level was minimal with maximum loading of the chimpanzee HBsAg with human immunoglobulin. HBsAg complexes could be dissociated by acid treatment. The HBsAg level was completely restored on day 7. Similar results were obtained for the preS1-containing particles that may represent the infectious viral particles in the chimpanzee serum. A mouse monoclonal anti-HBs (HBs.OT40) was found to compete with 9H9 in artificial immune complexes with the pre-treatment HBsAg from the chimpanzee. Used as a conjugate, HBs.OT40 yielded a maximum decrease in the signal in the 30 min sample compared to non-competing anti-HBs conjugates. This indicates binding of HBsAg with 9H9 in the circulation of the chimpanzee. Immune-complexed 4-7B could not be detected by its corresponding 4-7B peptide conjugate, probably due to its low concentration in the complexes. It is concluded that human monoclonal anti-HBs can effectively reduce the level of HBsAg in serum from this chronic carrier. Monoclonals 9H9 and 4-7B may complement each other due to their different mechanisms of inactivation, probably with higher efficiency than that monitored by our HBsAg screening assays. (+info)