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Lawrence Corey | |
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| Occupation(s) | American immunologist, virologist |
Lawrence Corey is an American immunologist and virologist known for his work in the development of antiviral therapies and vaccines, particularly for herpes simplex virus (HSV) and HIV/AIDS.
In the early 1980s, Corey worked with Nobel Prize-winning biochemist and pharmacologist Dr. Gertrude Elion to demonstrate that an antiviral that was selective and specific for a viral-specified enzyme could be safely and effectively administered to control a chronic viral infection (herpes simplex virus type 2 or HSV-2). Corey first conceived of, demonstrated the core concepts of, and directed line association between quantitative viral load reduction and clinical benefit using topical, intravenous and oral formulations of acyclovir in classic studies performed between 1980 and 1984. [1] [2] [3] Acyclovir was the first antiviral drug to get rapid approval from the FDA, and it was Corey's studies that defined its use in genital herpes. These studies led to the licensure for acyclovir in a wide variety of infections such as HSV-1, HSV-2 and varicella chickenpox virus, including the first use of an antiviral for daily long term use. Acyclovir and its derivatives valacyclovir and famciclovir are the most prescribed antivirals in the world: over 400 million people have HSV-2 infection. These early studies prompted the subsequent successful involvement of the pharmaceutical and medical sciences communities to develop effective antiviral therapy for HIV and Hepatitis B.
In 1987, Corey directed the NIH supported AIDS Clinical Trials Group (ACTG), which was established to test antivirals to HIV-1, and conducted pivotal clinical trials demonstrating the use of the antiretroviral drug AZT to reduce maternal-fetal transmission of HIV and the usefulness of combinations of antiretrovirals to prolong survival from HIV. [4] During this time, that laboratory demonstrated that HIV circulated in plasma well before the development of AIDS. [5] The ACTG subsequently demonstrated that the initiation of therapy early during asymptomatic stages of HIV infection reduced progression to HIV, [6] and that combinations of antiretrovirals (3>2>1 drug) were critical to the control of HIV replication and management; the result being that HIV control has enabled life expectancy to increase globally. [7] Triple combination therapy with two nucleosides and a protease inhibitor demonstrated a marked reduction in viral load, increase in CD4+ T-cell count and lowering of activation markers with the addition of the protease inhibitor. [8] The ACTG was the first to lead the integration of community members into clinical research activities. [9]
In the mid-1990s, Corey increasingly focused his work in the area of vaccine development, and in 1998 worked with the US National Institute of Allergy and Infectious Diseases to develop a global clinical trials group to speed the development of HIV vaccines. In 2002, Corey became the major driver in conceiving of the Global HIV Vaccine Enterprise. The Enterprise is one of the few scientific programs that is overseen by leaders of the major industrialized countries of the world.
One of Corey's major scientific initiatives has been to study and develop better therapy for the treatment and prevention of infectious disease associated cancers such as Kaposi sarcoma and Burkitt lymphoma. [10] In the mid-2000s, Corey launched a partnership between Fred Hutchinson Cancer Research Center and the Uganda Cancer Institute. [11] On July 30, 2010, Dr. Corey was named the fourth president of the Fred Hutchinson Cancer Research Center. [12] One of his major initiatives was to increase the strength of the Fred Hutch's translational research programs and its commitment to bring better therapies and preventions for cancer to the developing world. In May 2015, the Fred Hutch/UCI partnership led to the opening of the first comprehensive cancer center jointly constructed by US and African institutions in sub-Saharan Africa: the UCI-Fred Hutch Cancer Centre. [13] In 2013, as an outgrowth of his work in T-cell immunology, Corey became a cofounder of Juno Therapeutics, a company devoted to using genetically engineered T cells to fight cancer. [14]
Corey's early research dealt with herpes simplex viruses, and he headed several landmark studies defining the disease and leading the licensure of acyclovir and valacyclovir for its treatment. [15] [16] This included a study to reduce acquisition among sexual partners. Between 1988 and 1998, Corey published a series of key studies showing the association between infection with HSV-2 and HIV-1. [17] [18] These studies led to pilot and large sale clinical trials of anti-HSV-2 therapy to reduce HIV acquisition and transmission. [19] In 2000, Corey conducted the first discordant couple study using antiviral therapy for HSV-2. His publication in 2004 on reduction of transmission of HSV-2 was the first to demonstrate that antivirals could reduce transmission of infections to others (treatment as prevention), [20] a concept subsequently utilized by the HPTN 052 protocol team using continuous ART to reduce transmission of HIV to discordant couples. This latter approach is one of the current cornerstones of public health practices for reducing the morbidity and potentially the transmission of HIV-I. [21]
More recently, his research group has shown the importance of the mucosal immune system in controlling HSV reactivation, leading to current momentum to try to develop novel vaccines for treating genital herpes. Previously, the scientific consensus for HSV-2 pathogenesis was that virus reactivation was infrequent and determined by virus-neuronal interactions at the ganglion level and that most reactivations resulted in genital lesions.
Corey has been a central figure in the field of HIV vaccine development. [22] The HIV Vaccine Trials Network (HVTN) now includes investigators on five continents spanning more than 30 cities [23] and is leading the research for phase 1–3 clinical trials of candidate HIV vaccines globally. The HVTN as of 2018 is conducting 4 large scale efficacy trials in North America, South America and several countries in sub-Saharan Africa. On December 01, 2015 the work of Corey and HTVN scientists pursuing a vaccine to potentially halt HIV and AIDS was highlighted in an HBO/VICE special report titled "Countdown to Zero." [24]
Corey was a member of the editorial board of the New England Journal of Medicine. He is a fellow of the Infectious Diseases Society of America and a member of the American Epidemiological Society, American Society for Clinical Investigation, and the Association of American Physicians. In addition, he is the recipient of the Pan American Society's Clinical Virology Award, the American Sexually Transmitted Diseases Association's Parran Award, and the University of Michigan Medical School's Distinguished Alumnus Award. [25] In 2008, he was elected to the National Academy of Medicine and in 2012 elected a Member of the American Academy of Arts and Sciences. He has published over 900 scientific publications and editorials as of 2018.
Aciclovir, also known as acyclovir, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include prevention of cytomegalovirus infections following transplant and severe complications of Epstein–Barr virus infection. It can be taken by mouth, applied as a cream, or injected.
Valaciclovir, also spelled valacyclovir, is an antiviral medication used to treat outbreaks of herpes simplex or herpes zoster (shingles). It is also used to prevent cytomegalovirus following a kidney transplant in high risk cases. It is taken by mouth.
Viral encephalitis is inflammation of the brain parenchyma, called encephalitis, by a virus. The different forms of viral encephalitis are called viral encephalitides. It is the most common type of encephalitis and often occurs with viral meningitis. Encephalitic viruses first cause infection and replicate outside of the central nervous system (CNS), most reaching the CNS through the circulatory system and a minority from nerve endings toward the CNS. Once in the brain, the virus and the host's inflammatory response disrupt neural function, leading to illness and complications, many of which frequently are neurological in nature, such as impaired motor skills and altered behavior.
Famciclovir is a guanosine analogue antiviral drug used for the treatment of various herpesvirus infections, most commonly for herpes zoster (shingles). It is a prodrug form of penciclovir with improved oral bioavailability. Famciclovir is marketed under the trade name Famvir (Novartis).
Herpes simplex virus1 and 2, also known by their taxonomic names Human alphaherpesvirus 1 and Human alphaherpesvirus 2, are two members of the human Herpesviridae family, a set of viruses that produce viral infections in the majority of humans. Both HSV-1 and HSV-2 are very common and contagious. They can be spread when an infected person begins shedding the virus.
Genital herpes is a herpes infection of the genitals caused by the herpes simplex virus (HSV). Most people either have no or mild symptoms and thus do not know they are infected. When symptoms do occur, they typically include small blisters that break open to form painful ulcers. Flu-like symptoms, such as fever, aching, or swollen lymph nodes, may also occur. Onset is typically around 4 days after exposure with symptoms lasting up to 4 weeks. Once infected further outbreaks may occur but are generally milder.
Foscarnet (phosphonomethanoic acid), known by its brand name Foscavir, is an antiviral medication which is primarily used to treat viral infections involving the Herpesviridae family. It is classified as a pyrophosphate analog DNA polymerase inhibitor. Foscarnet is the conjugate base of a chemical compound with the formula HO2CPO3H2 (Trisodium phosphonoformate).
Herpes gladiatorum is one of the most infectious of herpes-caused diseases, and is transmissible by skin-to-skin contact. The disease was first described in the 1960s in the New England Journal of Medicine. It is caused by contagious infection with human herpes simplex virus type 1 (HSV-1), which more commonly causes oral herpes. Another strain, HSV-2 usually causes genital herpes, although the strains are very similar and either can cause herpes in any location.
The central nervous system (CNS) controls most of the functions of the body and mind. It comprises the brain, spinal cord and the nerve fibers that branch off to all parts of the body. The CNS viral diseases are caused by viruses that attack the CNS. Existing and emerging viral CNS infections are major sources of human morbidity and mortality.
Herpes simplex, often known simply as herpes, is a viral infection caused by the herpes simplex virus. Herpes infections are categorized by the area of the body that is infected. The two major types of herpes are oral herpes and genital herpes, though other forms also exist.
Neonatal herpes simplex, or simply neonatal herpes, is a herpes infection in a newborn baby, caused by the herpes simplex virus (HSV). It occurs mostly as a result of vertical transmission of the HSV from an affected mother to her baby. Types include skin, eye, and mouth herpes (SEM), disseminated herpes (DIS), and central nervous system herpes (CNS). Depending on the type, symptoms vary from a fever to small blisters, irritability, low body temperature, lethargy, breathing difficulty, and a large abdomen due to ascites or large liver. There may be red streaming eyes or no symptoms.
Herpes meningitis is inflammation of the meninges, the protective tissues surrounding the spinal cord and brain, due to infection from viruses of the Herpesviridae family - the most common amongst adults is HSV-2. Symptoms are self-limiting over 2 weeks with severe headache, nausea, vomiting, neck-stiffness, and photophobia. Herpes meningitis can cause Mollaret's meningitis, a form of recurrent meningitis. Lumbar puncture with cerebrospinal fluid results demonstrating aseptic meningitis pattern is necessary for diagnosis and polymerase chain reaction is used to detect viral presence. Although symptoms are self-limiting, treatment with antiviral medication may be recommended to prevent progression to Herpes Meningoencephalitis.
A cold sore is a type of herpes infection caused by the herpes simplex virus that affects primarily the lip. Symptoms typically include a burning pain followed by small blisters or sores. The first attack may also be accompanied by fever, sore throat, and enlarged lymph nodes. The rash usually heals within ten days, but the virus remains dormant in the trigeminal ganglion. The virus may periodically reactivate to create another outbreak of sores in the mouth or lip.
Herpes esophagitis is a viral infection of the esophagus caused by Herpes simplex virus (HSV).
Herpes simplex research includes all medical research that attempts to prevent, treat, or cure herpes, as well as fundamental research about the nature of herpes. Examples of particular herpes research include drug development, vaccines and genome editing. HSV-1 and HSV-2 are commonly thought of as oral and genital herpes respectively, but other members in the herpes family include chickenpox (varicella/zoster), cytomegalovirus, and Epstein-Barr virus. There are many more virus members that infect animals other than humans, some of which cause disease in companion animals or have economic impacts in the agriculture industry.
Herpetic simplex keratitis is a form of keratitis caused by recurrent herpes simplex virus (HSV) infection in the cornea.
Pritelivir is a direct-acting antiviral drug in development for the treatment of herpes simplex virus infections (HSV). This is particularly important in immune compromised patients. It is currently in Phase III clinical development by the German biopharmaceutical company AiCuris Anti-infective Cures AG. US FDA granted fast track designation for pritelivir in 2017 and breakthrough therapy designation 2020.
Gabriella Campadelli-Fiume is a virologist with a primary research focus on herpes simplex virus, fusion and viral entry. She is a retired professor of virology from the University of Bologna, Italy.
Stephen E. Straus was an American physician, immunologist, virologist and science administrator. He is particularly known for his research into human herpesviruses and chronic fatigue syndrome, and for his discovery of the autoimmune lymphoproliferative syndrome genetic disorder. He headed the Laboratory of Clinical Investigation of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), and served as the founding director of the NIH's National Center for Complementary and Alternative Medicine.
Human alphaherpesvirus 2 or Herpes simplex virus 2 is a species of virus in the genus Simplexvirus, subfamily Alphaherpesvirinae, family Herpesviridae, and order Herpesvirales.
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