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Order Picornavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
In mammalian cells, the VP60 gene was expressed by recombinant vaccinia (Bertagnoli et al. 1996b), myxoma (Bertagnoli et al. 1996a; Bárcena et al. 2000; Torres et al. 2000), or canarypox (Fischer et al. 1997) viruses. Although the problem of the possible VLP formation was not touched in these studies, the inoculations of recombinant viruses by different routes including oral ones allowed protection of rabbits against a challenge with virulent RHDV. Later, Yuan et al. (2013) performed protective DNA vaccination of rabbits with the gene encoding VP60 and demonstrated appearance of the native virion-like RHDV VLPs when the gene was expressed in rabbit kidney epithelial cell culture.
Neurological manifestations of West Nile virus
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Daniel E. Smith, J. David Beckham, Daniel M. Pastula, Kenneth L. Tyler
Effective human vaccines have been licensed for related flaviviruses including yellow fever virus and Japanese encephalitis virus, and a number of licensed equine WNV vaccines are commercially available. An inactivated WNV whole virus vaccine was developed for veterinary use in horses and became available in 2003 [84]. A recombinant canarypox vaccine soon followed [85].
AIDS and other acquired immunodeficiencies
Published in Gabriel Virella, Medical Immunology, 2019
John W. Sleasman, Gabriel Virella
Vaccines to prevent acquisition have been an even greater challenge. Recombinant viral particles made by inserting HIV glycoprotein genes in vaccinia virus or canary poxvirus genomes, for example, have been shown to induce neutralizing antibodies in both human and nonhuman primates. A vaccine trial testing a strategy to prime with a canary pox vector and three genetically engineered HIV genes (env, gag, and pol) termed ALVAC HIV (vCP1521), followed by a boost with an engineered gp120 protein (AIDSVAX B/E) has shown promise for providing protection to humans. Correlates of protection mapped to antibodies to variable regions 1 (V1) and 2 (V2). These studies provide promising evidence that an effective vaccine could be developed.
The current status of gene therapy in bladder cancer
Published in Expert Review of Anticancer Therapy, 2023
Côme Tholomier, Alberto Martini, Sharada Mokkapati, Colin P. Dinney
For years, adenoviral vectors have been one of the most well-characterized systems for gene delivery. The fiber knob of the adenovirus first binds to a cell surface coxsackie-adenoviral receptor (CAR), leading to intracellular incorporation of the virus and subsequent expression of the transgene. Absence of CAR in different bladder cancer cell lines is associated with resistance to adenoviral infection and gene therapy [54–56]. To overcome this limitation, researchers attempted to modulate CAR expression. Two groups showed that CAR gene activation can be promoted by histone acetylation in bladder cancer cells [57,58]. This provided the opportunity for pharmacological modulation of CAR expression by using histone deacetylase inhibitors such as valproic acid or sodium butyrate, to increase expression of CAR in T24 bladder cancer cell line, both in-vitro and in-vivo [59]. Similar findings have been described for a restricted canarypox viral vector, whereby intravesical instillation of oxychlorosene and poly-L-lysine enhanced transgene expression [60]. Moreover, reports on decreased expression of connexin 26 and loss of gap junction, essential for intercellular communication, have been reported in bladder cancer [61]. This led to a study showing improved suicide gene therapy with coadministration of HSV-Tk and connexin 26 [62]. Further research is warranted to identify novel viral receptors to improve gene therapy efficacy in clinical use.
Use of lentiviral vectors in vaccination
Published in Expert Review of Vaccines, 2021
Min-Wen Ku, Pierre Charneau, Laleh Majlessi
Viral vectors for vaccination have been derived from poxviruses, alphaviruses, and adenoviruses [4–7]. Poxviruses, including Modified Vaccinia virus Ankara (MVA), canarypox virus (ALVAC), and New York attenuated Vaccinia virus (NYVAC), were the first viral vectors to be evaluated in clinical trials [8]. The use of poxvirus-based vectors has been complicated due to their limited ability to induce memory T cells and the high prevalence of preexisting anti-vector immunity in human populations [9,10]. The use of alphavirus-based vectors is also limited because they induce strong transgene expression, leading to high toxicity for the host cells [10]. Compared to poxvirus-based vectors, adenoviral vectors trigger stronger T-cell responses, but these vectors, and especially those based on human adenoviruses, are targets of highly prevalent preexisting adaptive immunity which reduces their persistence in the host organism and thus decreases their immunogenicity [11]. Increasing the administered dose of an adenoviral vector can improve immunogenicity, but can also cause serious ‘grade 3’ adverse events, as recently demonstrated in a phase 2 trial of an Ad5-vectored COVID-19 vaccine [12]. Although such preexisting immunity can be circumvented by using animal-derived serotypes, there is evidence suggesting that such serotypes are less immunogenic and protective than Ad5 [13,14].
New avenues for therapeutic discovery against West Nile virus
Published in Expert Opinion on Drug Discovery, 2020
Alessandro Sinigaglia, Elektra Peta, Silvia Riccetti, Luisa Barzon
No WNV vaccines have been approved for use in humans so far [2,3]. At variance, inactivated vaccines, a canarypox-vectored vaccine expressing WNV prM/E, and a live chimera vaccine, generated from the YFV vaccine backbone and expressing WNV prM/E structural proteins (ChimeriVax-WN), have been licensed for use in horses [2,3]. ChimeriVax-WN was recalled from the market in 2010 because it was associated with severe anaphylactic reactions in horses due to an excipient in the vaccine. Several vaccine candidates for prevention of WNV infection in humans have been developed, using different technological platforms, and some have been tested in phase I and phase II clinical trials [2–9]. Vaccine candidates that have been tested in humans and nonhuman primates include hydrogen peroxide and formaldehyde inactivated whole virus vaccines (Hydrovax-001 and Inactivated WNV, respectively) [9], live, attenuated chimeric vaccines, i.e., ChimeriVax-WN02 [4–6] and rWN/DEN4Δ30 [7], a recombinant truncated E-protein vaccine [10,11], and DNA plasmid vaccines expressing WNV prM/E [8]. Next-generation adjuvants have been successfully used to improve the immunogenicity and protective efficacy of WNV vaccines in preclinical studies [12–14]. The results achieved so far in vaccine development are promising and support further research to generate an effective vaccine for human use. Issues that need to be addressed in vaccine development are the immunological cross-reactivity between flaviviruses and the associated risk of infection enhancement [3].