![]() Additionally, dl5-29 was shown to be effective in prevention of latent infection in guinea pigs irrespective of HSV-1 serostatus. The vaccine strain virus dl5-29 induces a protective immune response in vivo in mice and guinea pigs without either replication or establishment of latency. To address the lack of an effective vaccine, a replication defective HSV-2 vaccine strain virus ( dl5-29, which has since been re-derived and renamed ACAM529 ) has been constructed by deleting the U L5 and U L29 genes from the wild type virus. Since it is thought that there may be near-universal susceptibility to HSV-2 infection it is essential that there be some means for prevention of disease in sexually active populations. The degree of success has been varied, although at least in one case certain populations (HSV-1 and HSV-2 seronegative women) do appear to be protected. Examples of randomized, placebo-controlled vaccine trials in humans include inactivated, , live attenuated, ,, subunit, ,, ,, DNA and peptide approaches, which have been tested either in the prophylactic or therapeutic setting. estimate that the cost to treat HSV-2 infection could top $2.5 billion per year by 2015 with care centered around oral antiviral treatment and in some cases prevention of transmission with valacyclovir.īased upon the clear medical need for an effective HSV-2 vaccine, a number of approaches have been tested in the clinic (reviewed by ). As further evidence to the burden of this disease to US healthcare, Fisman et al. Worldwide there are an estimated 23 million new HSV-2 infections per annum, which underscores the clinical importance of this viral pathogen. During reactivation, the virus travels by anterograde transport to the skin surface where it can cause outward disease symptoms (genital ulcers, nonspecific symptoms or lesions and/or prodrome such as tingling, itching and pain) or may be asymptomatic. It then establishes latency by retrograde transport along nerve axons to the dorsal root ganglia. Initially, HSV-2 infects epithelial cells at the mucosal surface. HSV-2 is the primary cause of infectious ulcerative genital disease worldwide,. This does not alter the authors' adherence to all of the PLOS ONE policies on sharing those data and materials which are available. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: The authors have no support or funding to report.Ĭompeting interests: A provisional patent application has been filed by Sanofi Pasteur with the USPTO, application number 61/584,461. Received: OctoAccepted: JanuPublished: February 26, 2013Ĭopyright: © 2013 Mundle et al. PLoS ONE 8(2):Ĭincinnati Children's Hospital Medical Center, United States of America (2013) High-Purity Preparation of HSV-2 Vaccine Candidate ACAM529 Is Immunogenic and Efficacious In Vivo. Additionally, we describe a side-by-side comparison of chromatography-purified ACAM529 with sucrose cushion-purified ACAM529, which shows that both preparations are equally immunogenic and protective when tested in vivo.Ĭitation: Mundle ST, Hernandez H, Hamberger J, Catalan J, Zhou C, Stegalkina S, et al. The resultant virus retains infectivity and is ∼ 200-fold more pure with respect to host cell DNA and proteins than is ACAM529 purified by ultracentrifugation. ACAM529 may then be purified with respect to host cell DNA and proteins by a novel purification scheme, which includes a combination of endonuclease treatment, depth filtration, anion-exchange chromatography and ultrafiltration/diafiltration (UF/DF). ACAM529 can be harvested from infected cell culture of the trans-complementing cell line AV529 clone 19 (AV529-19) without mechanical cell disruption. Here we describe methods which serve as a major step towards preparation of ACAM529 which may be suitable for testing in humans. Immunization with dl5-29 was previously reported to be protective both in mice and in guinea pigs, however these studies were performed with vaccine that was purified using methods that cannot be scaled for manufacturing of clinical material. The replication-defective vaccine strain virus dl5-29 was re-derived using cells appropriate for GMP manufacturing and renamed ACAM529. For instance, the proportion of HSV-2 seropositive to seronegative adults is approximately 1 in 5 in the US and greater than 4 in 5 in some areas of sub-Saharan Africa. Infection by HSV-2 is life-long and is associated with significant cost to healthcare systems and social stigma despite the highly prevalent nature of the disease. Genital herpes is a sexually transmitted infection (STI) caused by herpes simplex virus 2 (HSV-2) and to a lesser extent herpes simplex virus 1 (HSV-1). ![]()
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