Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the terrorist attacks of September 11, 2001, and the anthrax exposures in the following weeks, concern that smallpox could be used as a biologic weapon has increased. Public health departments and the U.S. military have begun the process of vaccinating soldiers and civilian first-responders. Smallpox vaccination carries some serious risks: approximately one in 1 million primary vaccinees and one in 4 million revaccinees will die from adverse vaccine reactions. The most serious side effects of smallpox vaccine include progressive vaccinia, postvaccinial central nervous system disease, and eczema vaccinatum. Some of these reactions can be treated with vaccinia immune globulin or cidofovir. Proper patient screening and site care are essential. Family physicians must learn to screen potential vaccinees for contraindications (e.g., immunodeficiency, immunosuppression, certain skin and eye diseases, pregnancy, lactation, allergy to the vaccine or its components, moderate or severe intercurrent illness) and to treat vaccine-associated adverse reactions.
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PMID:Smallpox vaccine: contraindications, administration, and adverse reactions. 1367 38

Vaccinia viruses engineered to express foreign genes are powerful vectors for production of recombinant proteins. Originating from highly efficacious vaccines securing world-wide eradication of smallpox, the most appealing use of vaccinia vectors is to serve as vaccine delivery system for heterologous antigens. Concerns about the safety of vaccinia virus have been addressed by the development of vectors based on attenuated viruses. One of them, modified vaccinia virus Ankara (MVA) can be considered as current vaccinia virus strain of choice for clinical investigation. Historical development and use of MVA as vaccine against smallpox allowed to establish an extraordinary safety profile. MVA can be used under conditions of biosafety level 1 because of its avirulence and its deficiency to productively grow in human cells. In recent years significant progress has been made with regard to the development of MVA vector technologies. Compared to replication competent vaccinia viruses, MVA provides similar levels of recombinant gene expression even in nonpermissive cells. In animal models, MVA vaccines have been found immunogenic and protective against various infectious agents including immunodeficiency viruses, influenza, parainfluenza, measles virus, flaviviruses, or plasmodium parasites. By now first data from clinical trials are becoming available. In this article we briefly review history of MVA and state-of-the art technologies with regard to generation of recombinant MVA vaccines, and describe the progress to develop MVA vector vaccines against important infectious diseases.
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PMID:Vaccinia vectors as candidate vaccines: the development of modified vaccinia virus Ankara for antigen delivery. 1452 59

We have modeled smallpox vaccination with Dryvax (Wyeth) in rhesus macaques that had depletion of CD4(+) T cells induced by infection with simian immunodeficiency virus or simian/human immunodeficiency virus. Smallpox vaccination induced significantly larger skin lesions in immunocompromised macaques than in healthy macaques. Unexpectedly, "progressive vaccinia" was infrequent. Vaccination of immunocompromised macaques with the genetically-engineered, replication-deficient poxvirus NYVAC, before or after retrovirus infection, was safe and lessened the severity of Dryvax-induced skin lesions. Neutralizing antibodies to vaccinia were induced by NYVAC, even in macaques with severe CD4(+) T cell depletion, and their titers inversely correlated with the time to complete resolution of the skin lesions. Together, these results provide the proof of concept, in macaque models that mirror human immunodeficiency virus type 1 infection, that a prime-boost approach with a highly attenuated poxvirus followed by Dryvax increases the safety of smallpox vaccination, and they highlight the importance of neutralizing antibodies in protection against virulent poxvirus.
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PMID:Modeling a safer smallpox vaccination regimen, for human immunodeficiency virus type 1-infected patients, in immunocompromised macaques. 1455 89

The acyclic nucleoside phosphonates HPMPC (cidofovir), PMEA (adefovir), and PMPA (tenofovir) have proved to be effective in vitro (cell culture systems) and in vivo (animal models and clinical studies) against a wide variety of DNA virus and retrovirus infections: cidofovir against herpesvirus (herpes simplex virus types 1 and 2 varicella-zoster virus, cytomegalovirus [CMV], Epstein-Barr virus, and human herpesviruses 6, 7, and 8), polyomavirus, papillomavirus, adenovirus, and poxvirus (variola virus, cowpox virus, vaccinia virus, molluscum contagiosum virus, and orf virus) infections; adefovir against herpesvirus, hepadnavirus (human hepatitis B virus), and retrovirus (human immunodeficiency virus types 1 [HIV-1] and 2 [HIV-2], simian immunodeficiency virus, and feline immunodeficiency virus) infections; and tenofovir against both hepadnavirus and retrovirus infections. Cidofovir (Vistide) has been officially approved for the treatment of CMV retinitis in AIDS patients, tenofovir disoproxil fumarate (Viread) has been approved for the treatment of HIV infections (i.e., AIDS), and adefovir dipivoxil (Hepsera) has been approved for the treatment of chronic hepatitis B. Nephrotoxicity is the dose-limiting side effect for cidofovir (Vistide) when used intravenously (5 mg/kg); no toxic side effects have been described for adefovir dipivoxil and tenofovir disoproxil fumarate, at the approved doses (Hepsera at 10 mg orally daily and Viread at 300 mg orally daily).
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PMID:Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections. 1455 87

Although the transmission of certain viral infections (human immunodeficiency virus, hepatitis B and C viruses, and West Nile virus) through donated blood products is well described, the risk of transmitting vaccinia virus after smallpox vaccination is unknown. Blood samples from patients receiving the smallpox vaccine were obtained before vaccination; then from one-half of the study group on alternate days for each of the first 10 days after vaccination; then from all patients on days 14 and 21 after vaccination. Samples were analyzed by culture, polymerase chain reaction, and antigen detection (electrochemiluminescence) assay for the presence of vaccinia virus. Two hundred and twenty samples from 28 volunteers were processed by all 3 laboratory detection methods and all were negative for the presence of vaccinia virus (confidence interval, 0%-12.3%). Viremia with vaccinia virus after smallpox vaccination appears to be an uncommon occurrence.
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PMID:Lack of vaccinia viremia after smallpox vaccination. 1472 24

We identified 10 individuals who had undiagnosed human immunodeficiency virus type 1 (HIV-1) infection at the time of smallpox vaccination. Mean CD4 cell count was 483 cells/mm3 (range, 286-751 cells/mm3), and mean log10 plasma HIV-1 RNA load was 4.13 copies/cm3 (range, 2.54-5.16 copies/cm3). All vaccinees (3 primary and 7 repeat) had a normal, robust reaction without complications. Smallpox vaccine was well-tolerated in this small series of HIV-1-infected military personnel.
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PMID:Unintended smallpox vaccination of HIV-1-infected individuals in the United States military. 1512 48

The acyclic nucleoside phosphonates [HPMPC: cidofovir, Vistide; PMEA: adefovir dipivoxil, Hepsera; and PMPA: tenofovir, Viread] have proven to be effective in vitro (cell culture systems) and in vivo (animal models and clinical studies) against a wide variety of DNA virus and retrovirus infections, for example, cidofovir against herpesvirus [herpes simplex virus type 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus type 6, 7 and 8), polyoma-, papilloma-, adeno- and poxvirus (variola virus, cowpox virus, vaccinia virus, molluscum contagiosum virus and orf) infections; adefovir against herpesvirus, hepadnavirus [human hepatitis B virus] and retrovirus [HIV type-1 and 2, simian immunodeficiency virus and feline immunodeficiency virus] infections; and tenofovir against both hepadna- and retrovirus infections. Cidofovir has been officially approved for the treatment of cytomegalovirus retinitis in AIDS patients, tenofovir disoproxil fumarate (Viread) for the treatment of HIV infections (i.e., AIDS) and adefovir dipivoxil for the treatment of chronic hepatitis B.
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PMID:Potential of acyclic nucleoside phosphonates in the treatment of DNA virus and retrovirus infections. 1548

It is unknown whether smallpox vaccination would protect human immunodeficiency virus type 1 (HIV-1)-infected individuals, because helper CD4(+) cells, the targets of HIV-1 infection, are necessary for the induction of both adaptive CD8(+) cell and B cell responses. We have addressed this question in macaques and have demonstrated that, although smallpox vaccination is safe in immunodeficient macaques when it is preceded by immunization with highly attenuated vaccinia strains, the macaques were not protected against lethal monkeypox virus challenge if their CD4(+) cell count was <300 cells/mm(3). The lack of protection appeared to be associated with a defect in vaccinia-specific immunoglobulin (Ig) switching from IgM to IgG. Thus, vaccination strategies that bypass CD4(+) cell help are needed to elicit IgG antibodies with high affinity and adequate tissue distribution and to restore protection against smallpox in severely immunocompromised individuals.
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PMID:Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge. 1563 96

Recombinant modified vaccinia virus Ankara (MVA) is together with a few other attenuated viral vectors on the forefront of human immunodeficiency virus type 1 (HIV-1) vaccine development. As such, MVA-vectored vaccines are likely to be administered into immunocompromized individuals. Here, we demonstrated in a good laboratory practice study safety and biological clearance of candidate HIV-1 vaccine MVA.HIVA in simian immunodeficiency virus (SIV)-infected rhesus macaques and mice with a severe combined immunodeficiency (SCID) following an intradermal vaccine administration. In SIV-infected macaques, MVA.HIVA DNA was undetectable by nested PCR 6 weeks after dosing. In SCID mice, the MVA.HIVA vaccine was well tolerated and a positive PCR signal was only observed at the site of injection 49 days after dosing in four out of six mice, but even these sites were negative by day 81 post-injection. Therefore, the MVA.HIVA vaccine is considered safe for application in phase I clinical trials in HIV-1-infected human subjects. These results also contribute to the confidence of using MVA as a smallpox vaccine.
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PMID:Biodistribution and persistence of an MVA-vectored candidate HIV vaccine in SIV-infected rhesus macaques and SCID mice. 1567 Aug 87

Recent developments in nucleoside/nucleotide therapeutics and antiviral drug targets are described covering progress in the development of nucleoside/nucleotide mimetics for the treatment of influenza virus, human immunodeficiency virus type 1, hepatitis B and C virus, herpes virus infections; including herpes simplex virus, cytomegalovirus and varicella zoster virus infections, and the highly pathogenic poxviruses (variola, vaccinia and monkey pox) and filoviruses (Ebola and Marburg).
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PMID:Recent advances in antiviral nucleoside and nucleotide therapeutics. 1630 26


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