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Related post: SECTION Epidemiology Section INSTITUTE AND LOCATION NIAID, NTH, Bethesda, Buy Trecator-Sc MP 20892 TOTAL MAN-YEARS: 1.5 PROFESSIONAL: 0.6 0.9 CHECK APPROPRIATE BOX(ES) H (a) Human subjects □ (b) Human tissues □ (c) Neither (a1) Minors □ (a2) Interviews SUMMARY OF WORK (Use standard unreduced type. Do not exceed the space provided.) Rotaviruses are the single most important etiologic agents of severe diarrheal illness of infants and young children worldwide. Thus, there is an urgent need for a rotavirus vaccine that can prevent severe rotavirus diarrhea during the first two years of life when this illness is most serious. The "Jennerian" approach to vaccination, which involves use of a live vaccine virus strain derived from a non-human host, has been evaluated in clinical trials of (i) a bovine rotavirus by others, or (ii) a rhesus rotavirus (RRV) strain by the Epidemiology Section, LID. This strategy has had limited success because serotype- specific immunity against all 4 epidemiologically important human rotavirus serotypes (specified by outer capsid protein VP7) could not be achieved consistently in infants less than 6 months of age who had not Buy Cheap Trecator-Sc undergone prior rotavirus infection. Highly effective protection was observed when the simian RRV vaccine (VP7 serotype 3) was used to immunize young infants who were later exposed to human rotavirus strains of Purchase Trecator-Sc Online the same VP7 serotype. However, in other trials in which rotavirus with a VP7 serotype 1 predominated in the community, vaccine efficacy was variable. As a consequence, most recent clinical trials have employed a "modified Jennerian" approach in which a quadrivalent vaccine of broader antigenic coverage (that includes viruses of VP7 serotype 1, 2, 3, and 4) was used for immunization. This vaccine contains RRV (serotype 3) and reassortant rotaviruses containing 10 RRV genes and a single human rotavirus gene that encodes VP7 serotype 1, 2, or 4 specificity. In addition, a naturally attenuated human rotavirus strain, M37, with a VP7 specificity of serotype 1 and a unique VP4 Buy Trecator-Sc Online specificity shared by other neonatal strains belonging to VP7 serotype 1, 2, 3, or 4, is also under evaluation. Phase 1 trials of the human rotavirus M37 live vaccine have been completed successfully. The M37 rotavirus vaccine was shown to be safe and immunogenic in a clinical study involving 150 young infants (2-4 months of age) and as a consequence phase 2 efficacy trials are now in progress. I 11-57 — PHS 6040 (Rev. 1/84) oPoiu-tn PROJECT NUMBER DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT Z01 AI 00342-09 LID PERIOD COVERED October 1, 1989 to September 30, 1990 TITLE OF PROJECT (80 characters or less. Title must lit on one line between the borders) Studies of Gastroenteritis Viruses by Electron Microscopy PRINCIPAL INVESTIGATOR (List other professional personnel below the Pnncipal Investigator.) (Name, title, laboratory, and institute affiliation) PI: Albert Z. Kapikian, M.D. Head, Epid. Section LID, NIAID COOPERATING UNITS (if any) LAB/BRANCH Laboratory of Infectious Diseases SECTION Epidemiology Section INSTITUTE AND LOCATION NIAID, NTH, Bethesda, MP 20892 TOTAL MAN-YEARS: 0.2 PROFESSIONAL: 0.1 0.1 CHECK APPROPRIATE BOX(ES) B (a) Human subjects S (b) Human tissues □ (c) Neither □ (al) Minors □ (a2) Interviews SUMMARY OF WORK (Use standard unreduced type. Do not exceed the space provided ) The electron microscope has been a mainstay in the study of gastroenteritis viruses. Two major groups of gastroenteritis viruses—the 27nm Norwalk virus and the 70nm human rotaviruses- -were discovered at NTH and in Australia, respectively, (as well Purchase Trecator-Sc as the hepatitis A virus at NTH, in collaboration with the Hepatitis Section) with the use of the electron microscope. It is remarkable that in this era of tissue culture virology, these agents were discovered initially without the use of an in vitro tissue culture system, since they could not be grown directly from clinical specimens in cell culture. We have applied the term, "direct virology," to this method of examining viruses from clinical specimens by electron microscopy. Although second and third generation tests have been developed for the detection of the Norwalk group of viruses and the rotaviruses, the electron microscope is still an indispensable tool for the study of these gastroenteritis viruses. It is also the most rapid diagnostic tool for detection of rotavirus from a clinical specimen and is the only method available for diagnosing infection with certain 27nm viruses associated with epidemic nonbacterial gastroenteritis. It also is important for: (i) providing direct visualization of virus particles from density gradients (to establish their morphologic appearance, e.g., single or double capsid, integrity of capsid structure, and to determine presence or absence of particles or their quantitation); (ii) providing direct visualization of particles from clinical specimens to determine their identity, if feasible; (iii) attempting to visualize the site of activity of antibodies such as monoclonal Order Trecator-Sc Online antibodies or recombinant virus induced antibodies; and (iv) serologic studies performed by immune electron microscopy to determine the antigenic relationships of fastidious gastroenteritis agents that cannot be propagated in cell culture such as the human group C rotaviruses, and the Norwalk group of agents. However, its most important and creative Order Trecator-Sc role is in its application to the detection of new, heretofore unknown, agents of acute infectious gastroenteritis and other diseases as well. 11-58 PHS 6040 (Rev. 1/&4) GPO t!4-»H DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER
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