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Influenza vaccination policies of 28 European countries were compared with those of the US Immunization Practices Advisory Committee. Twenty-four of 28 (86%) European countries had immunization policies for influenza. European and US recommendations were in complete agreement concerning immunization of those with heart and lung disease. Within Europe there was 81-86% agreement concerning immunization...
Influenza A virus neuraminidase (NA) from A/Udorn/72 (H3N2) was expressed by recombinant baculovirus-infected insects. The recombinant NA was enzymatically active. Enzyme activity was neutralized by polyclonal antisera raised against virion-extracted NA. NA produced in whole insects by a baculovirus expression system is antigenically indistinguishable from virion NA by polyclonal antisera in functional...
Previously, we reported 12 synthetic T- and B-cell recognition regions representing surface areas of the hemagglutinin (HA) of X31 influenza virus. In the present study, four of these peptides were examined in Balb/c mice for their ability to produce protective immunity against lethal infection with a dose equivalent to 10 LD 50 of influenza virus. These peptides corresponded to the...
Healthy adult volunteers were immunized by parenteral or oral routes with trivalent inactivated influenza vaccine (A/Chile/1/83 (H1N1), A/Mississippi/1/85 (H3N2), and B/Ann Arbor/1/86), or intranasally with live attenuated, cold-adapted influenza type A/Texas/1/85 (H1N1) reassortant virus. In all volunteers, cells spontaneously secreting IgA, IgG or IgM antibodies specific to influenza virus were...
We have investigated the potential of the conserved transmembrane M2 protein of influenza A/Ann Arbor/6/60 virus, expressed by a baculovirus recombinant, to induce protective immunity in BALB/c mice. Vaccination of mice with M2 shortened the duration of virus shedding and protected mice from a lethal infection with A/Ann Arbor/6/60 virus but not B/Ann Arbor/1/55 virus, suggesting that the protection...
Weanling ferrets were inoculated intranasally with either wild-type or receptor-variant clones of influenza A/Memphis/102/72 to determine if changes in receptor specificity influence virulence of influenza virus infection. Over the 5 days after inoculation, receptor-variant inoculated ferrets had a lower mean elevation in body temperature, greater weight gain and less sneezing than the wild-type...
Pre- and post-vaccination sera from 19 volunteers were analysed by the haemagglutination inhibition (HI) test, virus neutralization (VN) assay and avidity enzyme-linked immuno-sorbent assay (ELISA). The sera were tested against the three strains in a commercial inactivated influenza vaccine; A/Beijing/353/89 (H3N2); A/Taiwan/1/86 (H1N1) and B/Yamagatal/16/88. Additionally, a range of earlier strains...
Antibody responses and protection were studied in BALB/c mice immunized orally with formalin-inactivated influenza viruses (A/PR/8/34) combined with cholera toxin B subunit as adjuvant. Influenza virus-specific IgA as well as IgG antibody responses were induced in the mice, depending on the oral dosage frequency. The oral immunization by multiple doses resulted in reduction of viral replication...
The pre-clinical efficacy of DNA vaccines has been demonstrated in a number of animal models, but more limited data exist regarding their immunogenicity in non-human primates. The studies described below demonstrate that DNA vaccines in reasonable dosages encoding a variety of viral proteins could result in the generation of antibodies, neutralizing antibodies, or cytotoxic T lymphocytes in primates...
Two fundamentally different approaches to vaccination of BALB/c mice with the hemagglutinin (HA) of A/Equine/Kentucky/1/81 (H3N8) (Eq/KY) were evaluated, that is, administration of HA protein vs administration of HA-encoding DNA. Each vaccine was tested for its immunogenicity and ability to provide protection from homologous virus challenge. HA protein was synthesized in vitro by infection of Sf21...
Synthesis of the carbohydrate structure Gala1-3Galβ1-4GlcNAc-R (termed the α-gal epitope) on viral glycoproteins is of interest because of the large amounts of natural antibody (anti-Gal) produced in humans against this epitope. The presence of α-gal epitopes on inactivated virus or subviral vaccines is likely to enhance vaccine immunogenicity through in vivo complexing with anti-Gal and the subsequent...
The purpose of the present study was to produce an influenza A H2N2 donor virus from which an attenuating PB2 gene bearing three discrete temperature sensitive (ts) mutations could be readily transferred to currently epidemic influenza A H1N1 and H3N2 viruses via genetic reassortment. An influenza A transfectant virus was first produced that contained site-directed ts mutations at amino acids 112,...
Previous studies have demonstrated that the ability of γ-irradiated whole influenza virus to prime for specific anti-influenza antibody responses was dramatically enhanced when delivered in a complex with chicken red blood cell ghosts (cRBC). The purpose of this study was to investigate the effect of increasing the dose of gamma irradiation used to inactivate A/Queensland/6/72 virus on the ability...
Cellular as well as humoral immune reactivity were studied in healthy young (<30 years; n = 12) and older (>65 years; n = 12) individuals before as well as 1 month after immunization with a trivalent whole virus influenza vaccine. Before vaccination, peripheral blood mononuclear cell proliferation in response to in vitro stimulation with each of the virus strains was low in both groups. No...
Introduction of influenza viruses with gene segments of avian origin into the human population may result in the emergence of new pathogenic human influenza viruses. The recent infection of a 3-year-old boy with an influenza A (H5N1) virus of avian origin can be considered as an example of such an event. However, this virus, influenza A/Hong Kong/156/97 (H5N1) and the 17 additional H5N1 viruses...
Bacterial DNA causes B cell proliferation, immunoglobulin secretion, and Th1-like cytokine secretion, due to unmethylated CpG dinucleotides in particular base contexts (CpG motifs), which are far more common in bacterial DNA than in vertebrate DNA. Synthetic oligodeoxynucleotides (ODN) containing CpG motifs also trigger immune activation, suggesting possible utility as vaccine enhancers. Mice systemically...
Bacterial DNA causes B cell proliferation, immunoglobulin secretion, and Th1-like cytokine secretion, due to unmethylated CpG dinucleotides in particular base contexts (CpG motifs), which are far more common in bacterial DNA than in vertebrate DNA. Synthetic oligodeoxynucleotides (ODN) containing CpG motifs also trigger immune activation, suggesting possible utility as vaccine enhancers. Mice systemically...
Inactivated alum-adjuvanted conventional equine influenza virus vaccines are of poor efficacy and offer limited short-term protection against infection. In sharp contrast, natural infection with equine influenza virus confers long-term protective immunity. In order to identify the protective immune responses to equine influenza virus, the influenza virus-specific IgA, IgGa, IgGb, IgGc and IgG(T)...
Two quite different adjuvants, currently under development for use in humans, have been examined for their effects on the magnitude and type of immunity elicited in response to inactivated influenza vaccine. Immunostimulating complexes (ISCOM TM adjuvant) contain the saponin ISCOPREP TM 703, and SPT is an oil-in-water emulsion of squalane, non-ionic block copolymer (L121)...
We proposed a strategy (cassette theory) in which non-binding peptides for murine major histocompatibility complex (MHC) class II molecules are introduced into a MHC-binding component to render the resultant hybrid peptides bound to the MHC and thus immunogenic in animals carrying the relevant MHC. It was shown that 46F/HA127-133/54A(18mer) peptide which was prepared by introducing hemagglutinin (HA)127-133...
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