A Lentiviral Vector-Based, Herpes Simplex Virus 1 (HSV-1) Glycoprotein B Vaccine Affords Cross-Protection against HSV-1 and HSV-2 Genital Infections

Genital herpes is caused by herpes simplex virus 1 (HSV-1) and HSV-2, and its incidence is constantly increasing in the human population. Regardless of the clinical manifestation, HSV-1 and HSV-2 infections are highly transmissible to sexual partners and enhance susceptibility to other sexually transmitted infections. An effective vaccine is not yet available. Here, HSV-1 glycoprotein B (gB1) was delivered by a feline immunodeficiency virus (FIV) vector and tested against HSV-1 and HSV-2 vaginal challenges in C57BL/6 mice. The gB1 vaccine elicited cross-neutralizing antibodies and cell-mediated responses that protected 100 and 75% animals from HSV-1- and HSV-2-associated severe disease, respectively. Two of the eight fully protected vaccinees underwent subclinical HSV-2 infection, as demonstrated by deep immunosuppression and other analyses. Finally, vaccination prevented death in 83% of the animals challenged with a HSV-2 dose that killed 78 and 100% naive and mock-vaccinated controls, respectively. Since this FLY vector can accommodate two or more HSV immunogens, this vaccine has ample potential for improvement and may become a candidate for the development of a truly effective vaccine against genital herpes

Capitolo 44 Herpesviridae

In questo capitolo, che fa parte di un libro di Testo Universitario, si descrivono gli Herpesvirus che sono virus molto diffusi in natura e possono infettare la maggior parte delle specie animali, dai pesci ai mammiferi, per un totale di almeno 130 specie differenti. Gli Herpesvirus che interessano la medicina umana sono stati classificati in tre sottofamiglie: α, β e γ in base a proprietà replicative e strutturali, sede d’infezione e sede di latenza

Virologia

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HSV-1-derived helper-independent defective vectors, replicating vectors and amplicon vectors, for the treatment of brain diseases.

HSV-1 is a neurotropic virus that displays several important adaptations to the nervous system of the host organism, each of which can be rationally exploited in the design of gene therapy vectors for neurological applications. Replication-incompetent (replication-defective) helper-independent recombinant vectors are nontoxic tools for gene transfer that preserve most of the neurotropic features of HSV-1, particularly the ability to express genes after establishing latent infections, and are thus proficient candidates for therapeutic gene transfer in neurons. A clinical trial with the use of a replication-incompetent vector, NP-2 (Diamyd Inc), for the treatment of pain has been initiated. Attenuated replication-competent (oncolytic) vectors are becoming suitable and powerful tools to eradicate brain tumors, such as malignant gliomas, as a result of the ability to replicate and spread only within the tumor mass. Some attenuated replication-competent vectors, such as G-207 and HSV-1716 (Crusade Laboratories Ltd), have been used in clinical trials for the treatment of cancers including recurrent malignant glioma. Helper-dependent amplicon vector technology takes advantage of the capacity of the virus particle to accommodate < or = 150 Kbp of foreign DNA, enabling these vectors to deliver complete genomic loci to the nucleus of mammalian cells, making amplicons particularly useful agents in protocols that require stable and physiological transgene expression. However, difficulties in obtaining large stocks of helper-free amplicons continue to limit the use of these vectors in the clini

Vettori erpetici per la terapia genica di patologie del sistema nervoso centrale.

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