Vaccine
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Vaccination of poultry against avian influenza is of high priority, in particular after the dramatic spread of subtype H5N1 in Asia, Africa and Europe. Newcastle disease virus (NDV) has been developed as a vector for the expression of the main immunogen of avian influenza virus, hemagglutinin (HA). An NDV vector based vaccine has several advantages. ⋯ Therefore, a new NDV recombinant (NDVH5Vm) was generated which expresses the H5 protein of HPAIV A/chicken/Vietnam/P41/05 (H5N1). This recombinant virus protected chickens against lethal infection with HPAIV H5N1 (Vietnam) already after one immunization. Our data thus show that application of a vector-based vaccine in the control of influenza may require adaptation of the vaccine to currently circulating viruses.
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Toll-like receptors (TLRs) represent the critical "bridge" between innate and adaptive immunity to viral pathogens. We hypothesized that single nucleotide polymorphisms (SNPs) that potentially influence the expression/function of TLRs and their associated intracellular signaling molecules contribute to variations in humoral and cellular immunity to measles vaccine. We genotyped 190 randomly selected subjects (12-18 years old), previously vaccinated with two doses of measles, for known SNPs in TLR 2, 3, 4, 5, 6, 7, 8 and 9, and their associated intracellular signaling genes. ⋯ In addition, SNPs in MyD88 and MD2, intracellular molecules that associate with TLRs, also demonstrated associations with variations in antibody and IL-10 production (p
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Avian-to-human transmission of the high pathogenicity (HP) H7N7 subtype avian influenza viruses in the Netherlands during 2003 caused zoonotic infections in 89 people, including a case of acute fatal respiratory distress syndrome. Public health emergency preparedness against H7N7 avian influenza viruses with pandemic potential includes the development of vaccine candidate viruses. In order to develop a high growth reassortant vaccine candidate virus, low pathogenicity (LP) A/mallard/Netherlands/12/2000 (H7N3) and A/mallard/Netherlands/2/2000 (H10N7) strains were selected as donors of the H7 haemagglutinin and N7 neuraminidase genes, respectively. ⋯ Mice immunized with formalin inactivated (FI) H7N7/PR8 whole virus vaccine with or without aluminum hydroxide adjuvant conferred clinical protection from mortality and reduced pulmonary replication of the NL219 challenge virus. The FI H7N7/PR8 whole virus vaccine also afforded cross-protection in mice at the pulmonary level against antigenically distinct North American LP A/Canada/444/04 (H7N3) human isolate. The vaccine candidate virus satisfied the agricultural safety requirements for chickens, proved safe in mice, and has entered in phase-I human clinical trial in the United States.
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Development of vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is crucial in the prevention of SARS reemergence. The receptor-binding domain (RBD) of SARS-CoV spike (S) protein is an important target in developing safe and effective SARS vaccines. Our previous study has demonstrated that vaccination with adeno-associated virus encoding RBD (RBD-rAAV) induces high titer of neutralizing antibodies. ⋯ Compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide (RBD-Pep) boost induced similar levels of Th1 and neutralizing antibody responses that protected the vaccinated mice from subsequent SARS-CoV challenge, but stronger Th2 and CTL responses. No significant immune responses and protective effects were detected in mice vaccinated with RBD-Pep or blank AAV alone. Since T cell epitopes are highly conserved and boosting with peptides may induce the production of effector memory T cells, which may be effective against viruses with mutations in the neutralizing epitopes, our results suggest that the vaccination protocol used may be ideal for providing effective, broad and long-term protection against SARS-CoV infection.
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Adjuvants enhance antibody response against vaccination. We compared the ability of MF59-adjuvanted and non-adjuvanted subunit influenza vaccines, containing A/Wyoming/3/03(H3N2), to confer cross-protection against four consecutive drifted strains in the elderly. Neutralizing and haemagglutination-inhibiting antibody were measured. ⋯ A/Panama/2007/99(H3N2) circulated widely during the previous 5 years and was included in vaccines over four consecutive seasons. Broader serological protection against drifted strains that circulated 1 and 2 years after vaccination with A/Wyoming/3/03(H3N2) was observed with MF59-adjuvanted vaccine. Thus, MF59-adjuvanted vaccine confers greater immunogenicity than non-adjuvanted vaccines in vulnerable populations.