DNA Virus Vaccine Safety Issues: Contamination and Viral Latency

Principal Investigator: Philip R. Krause, MD
Office / Division / Lab: OVRR / DVP / LDV

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Overview

Public Health Issue: The impressive public and personal health benefits of vaccines depend on public confidence that these products are safe. DNA viruses are particularly important both as licensed vaccine components and as potential contaminants, because of their ability to establish life-long latency, with the capacity to later reactivate in vaccine recipients. Thus, it is critical to develop improved methods to evaluate viral latency potential in DNA virus vaccines, as well as improved means to evaluate risk of latent DNA viruses in cell substrates.

Regulatory Contribution: It is critical to assure that the cells used to produce vaccines are not contaminated with undesired viruses, and that the vaccines themselves are free of unintended viruses. Cell contaminants of concern may include both infectious viruses and latent viruses that may become infectious during the manufacturing process. This program directly supports regulatory decision-making and guidance development related to preventing (and detecting) contamination, and assuring the safety of DNA virus vaccines.

Research Approach: The goals of this program are to develop new molecular techniques to assure the absence of contaminants in vaccines and in new cell types (which will help to support the development of a new generation of vaccines), and to contribute to an.increased understanding of viral latency, (which will increase the availability of tests to detect latent viruses, and will increase understanding of the impact of these viruses on product safety).

Mission Relevance and Outcomes: These studies will provide the knowledge and tools for evaluating and supporting the development of safe vaccines.

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Publications

J Virol 2009 Feb;83(3):1433-42
Novel less-abundant viral microRNAs encoded by herpes simplex virus 2 latency-associated transcript and their roles in regulating ICP34.5 and ICP0 mRNAs.
Tang S, Patel A, Krause PR

J Virol Methods 2008 Sep;152(1-2):18-24
Universal virus detection by degenerate-oligonucleotide primed polymerase chain reaction of purified viral nucleic acids.
Nanda S, Jayan G, Voulgaropoulou F, Sierra-Honigmann AM, Uhlenhaut C, McWatters BJ, Patel A, Krause PR

Proc Natl Acad Sci U S A 2008 Aug 5;105(31):10931-6
An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor.
Tang S, Bertke AS, Patel A, Wang K, Cohen JI, Krause PR

MMWR Recomm Rep 2008 Jun 6;57(RR-5):1-30
Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP).
Harpaz R, Ortega-Sanchez IR, Seward JF; Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC)

Clin Chim Acta 2008 Jan;387(1-2):145-9
Pseudohyperphosphatemia associated with high-dose liposomal amphotericin B therapy.
Lane JW, Rehak NN, Hortin GL, Zaoutis T, Krause PR, Walsh TJ

J Virol 2007 Jun;81(12):6605-1
Herpes Simplex Virus Latency-Associated Transcript (LAT) Sequence Downstream of the Promoter Influences Type-Specific Reactivation and Viral Neurotropism.
Bertke AS, Patel A, Krause PR

J Virol 2007 Feb;81(4):1872-8
HSV-2 Establishes Latent Infection In a Different Population of Ganglionic Neurons than HSV-1: Role of LAT.
Margolis TP, Imai Y, Yang L, Vallas V, Krause PR

Clin Infect Dis 2005 Sep 1;41(5):676-80
Development of herpes simplex virus disease in patients who are receiving cidofovir.
Wyles DL, Patel A, Madinger N, Bessesen M, Krause PR, Weinberg A

Virus Genes 2004 Jan;28(1):71-83
Simian cytomegalovirus encodes five rapidly evolving chemokine receptor homologues.
Sahagun-Ruiz A, Sierra-Honigmann AM, Krause P, Murphy PM