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B lineage mismatch prompted introduction of quadri-valent influenza vaccines (QIV) with two influenza B viruses representing distinct antigenic lineages. To explore the impact on antibody induction and vaccine effectiveness predicted from antibody (VEab), we performed a systematic literature search on immunogenicity studies conducted to assess antibody superiority of QIV over trivalent influenza vaccine...
Infections with low pathogenic avian influenza (LPAI) A(H7N9) viruses have caused more than 100 hospitalized human cases of severe influenza in China since February 2013 with a case fatality rate exceeding 25%. Most of these human infections presented with severe viral pneumonia, while limited information is available currently on the occurrence of mild and subclinical cases. In the present study,...
As infectious diseases cause approximately 25% of the annual global mortality, vaccines are found to be a time proven and promising response to infectious disease need. However, like for pharmaceutical small molecules, vaccine development is lengthy, risky and resource demanding. Faced with an attrition rate estimated around 80%, key opinion leaders were interviewed with the question: is there a recipe...
Gold dimensions of pharmaceutical drug development indicate that it takes on average 11.9 years, with an investment around US$ 0.8 Billion, to launch one product on the market. Furthermore, approximately 22% of the drug candidates successfully complete clinical testing. These universally acknowledged proportions largely originate from one single, much cited publication; Dimasi et al. [5]. However...
Several inactivated influenza vaccine formulations for systemic administration in man are currently available for annual (seasonal) immunization: split virus and subunit (either plain-aqueous, or virosomal, or adjuvanted by MF59). From a literature search covering the period 1978–2009, 33 articles could be identified, which described randomized clinical trials comparing at least two of the four vaccine...
The feasibility of a single-shot, low-dose vaccination against pandemic influenza was investigated. The immunogenicity and safety of whole inactivated, cell culture-derived H5N1 virus plus CoVaccine HT™ as adjuvant was tested in various animal species. In ferrets, doses of 4.0 and 7.5μg H5N1 (NIBRG-14; A/Vietnam/1194/04; clade 1) without adjuvant gave low geometric mean haemagglutination inhibition...
Reverse genetics can be used to produce recombinant influenza A viruses containing virtually every desired combination of hemagglutinin (HA) and neuraminidase (NA) genes using the virus backbone of choice. Here, a repository of plasmids and recombinant viruses representing all contemporary Eurasian HA and NA subtypes, H1–H16 and N1–N9, was established. HA and NA genes were selected based on sequence...
A candidate influenza H5N1 vaccine based on cell-culture-derived whole inactivated virus and the novel adjuvant CoVaccineHT™ was evaluated in vitro and in vivo. To this end, mice were vaccinated with the whole inactivated influenza A/H5N1 virus vaccine with and without CoVaccineHT™ and virus-specific antibody and cellular immune responses were assessed. The addition of CoVaccineHT™ increased virus...
Highly pathogenic avian influenza viruses of the H5N1 subtype are responsible for an increasing number of infections in humans since 2003. More than 60% of the infections is lethal and new infections are reported frequently. In the light of the pandemic threat caused by these events the rapid availability of safe and effective vaccines is desirable. Modified vaccinia virus Ankara (MVA) expressing...
The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1...
Examples of vaccine-induced enhancement of susceptibility to virus infection or of aberrant viral pathogenesis have been documented for infections by members of different virus families. Several mechanisms, many of which still are poorly understood, are at the basis of this phenomenon. Vaccine development for lentivirus infections in general, and for HIV/AIDS in particular, has been little successful...
In order to assess the level of protection against a lethal influenza virus infection provided by a primary infection with a virus strain of another subtype, C57BL/6 mice were infected with the sublethal influenza virus X-31 (H3N2) and subsequently challenged with the lethal strain A/PR/8/34 (H1N1). The outcome of the challenge infection was compared with that in mice that did not experience an infection...
The use of cytotoxic T lymphocyte (CTL)-inducing vaccines could afford both homo- and heterosubtypic immunity. However, amino acid variation in CTL epitopes associated with escape from CTL-mediated immunity might undermine the use of these vaccines. To assess the impact of amino acid substitutions in highly conserved epitopes on viral fitness and recognition by specific CTL, we performed a mutational...
In the process of developing a subunit vaccine against phocid herpesvirus type 1, we have cloned and expressed the glycoproteins B and D (gB and gD) of phicid herpesvirus type 1, using an eukaryotic baculovirus expression system. To establish the proof of concept, candidate iscom vaccines based on these affinity-purified proteins either alone or in combination, were tested for their immunogenicity...
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