Safety requirements for maintenance and distribution of transgenic mice susceptible to human viruses: the example of poliovirus-susceptible transgenic mice.
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Animals↗
Biomedical subjects
Y Ghendon
Publications and source records attributed to Y Ghendon.
Introduction to pandemic influenza through history.
For the past 400 years, epidemics resembling influenza have been recorded in many countries. Epidemics from as early as the 16th Century in England and the 18th Century in the USA are recognizable as influenza, even in the absences of precise knowledge of their causative agents.
Disease Outbreaks↗
Influenza vaccines: a main problem in control of pandemics.
The optimal strategy for control of pandemic influenza is early vaccination with influenza vaccine produced from influenza pandemic strains. However, for pandemic control, vaccine improvements are essential and should include quicker ways of manufacturing and testing of vaccine as well as flexibility on the part of licensing bodies. The production of mass doses of monovalent vaccine in a short time can be more realistic if egg independent production technology can be adopted. In this respect production of an influenza vaccine on a stable cell line can solve many of the problems in increased production of influenza vaccine. But the difficulty with influenza vaccines is that the yield of human influenza viruses on tissue culture is much lower than in embryonated eggs. A new high-yield donor is needed for construction of recombinants with a new pandemic strain, which can replicate in a stable cell line with high titre. The live influenza vaccine may be the most appropriate for prophylaxis of influenza pandemic, as the implementation of this vaccine for mass vaccination is simpler than of inactivated influenza vaccine, and this vaccine, after one immunization of unprime persons, induces local mucocosa immunity which plays an important role in the protection against influenza.
Aged↗
Recommendations of the 7th European Meeting of Influenza and Its Prevention.
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Disease Outbreaks↗
Interrupting the transmission of wild polioviruses with vaccines: immunological considerations.
In 1988 the World Health Assembly set the goal of global poliomyelitis eradication by the year 2000. Substantial progress has been made, and 143 countries reported no poliomyelitis cases associated with the wild virus in 1993. This article reviews the immunological considerations relevant to interrupting the transmission of wild polioviruses with vaccines. Although serum immunity prevents poliomyelitis in the individual, it is local immunity that is important in preventing the transmission of polioviruses in the community. Natural infection and vaccination with oral polioviruses vaccine (OPV) produce local immunity in the intestine and the nasopharynx in about 70-80% of individuals. In contrast, inactivated poliovirus vaccine (IPV) produces local intestinal immunity in only 20-30% of the individuals. With either vaccine, however, a substantial proportion of the immunized population can transmit the wild virus. Moreover, although serum immunity is long-lasting, limited data suggest that local immunity may not be as persistent. To interrupt the transmission of wild polioviruses efforts should be made to achieve and sustain high levels of poliovirus vaccine coverage. Recent outbreaks show that wild poliovirus poses a risk for unimmunized individuals, even when overall coverage levels are high. Delivery of poliovirus vaccine to hard-to-reach populations will be of increasing importance as countries progress toward the final stages of poliomyelitis eradication. The immunization status of persons from poliomyelitis-free countries should be updated prior to travel to poliomyelitis-endemic areas.
Antibodies, Viral↗
WHO recommendation on potential use of new poliomyelitis vaccines.
Due to the intensive use of Sabin attenuated oral poliomyelitis vaccine, the incidence of poliomyelitis is continuing to decline, particularly in the Americas and Western Europe. In some developing countries, the use of trivalent attenuated vaccine may, however, sometimes produce sub-optimal antibody responses. Moreover, rare cases of vaccine-associated paralytical poliomyelitis could become increasingly prevalent, especially in countries that achieve control of the wild-type polioviruses. Recent progress in understanding the molecular biology and mechanisms of attenuation of polioviruses has suggested several possible approaches to solving some of these problems with improved attenuated poliovirus strains. During WHO meetings discussions took place on the broad scientific and ethical criteria that would justify submitting new attenuated oral poliomyelitis vaccine candidates to different levels of testing in laboratories and in humans.
Adult↗
Influenza--its impact and control.
Influenza is an underestimated public health problem. Epidemics spread rapidly from country to country and may affect as many as 500 million people across the world in a moderate influenza year. The disease, particularly influenza A, kills and the new influenza viruses which appeared in 1957 (Asian influenza) and 1968 (Hong Kong) are estimated to have caused at least 100,000 deaths in the United States of America. Deaths from influenza also occur in years when there is no new virus; at least 10,000 excess deaths have been documented in the United States during each of 18 different epidemics recorded from 1957 to 1985. Although most deaths are among the elderly, influenza occurs in all age groups with repercussions in schools and work places, and on hospital resources, at a high cost to society. As many as 79-80% of influenza cases can be prevented when the virus inducing the outbreak and the virus used in the influenza vaccine are closely related. Preventing 80% of cases would correspond in the United States to a saving of US $2.5 billion. People at the greatest risk of influenza-related complications are adults and children with chronic disorders of the pulmonary or cardiovascular systems, residents of nursing homes and of facilities for patients with chronic medical conditions. Other priority groups for vaccination are those at moderate risk of influenza-related complications such as healthy elderly persons, people with chronic metabolic diseases, children and teenagers on long-term aspirin therapy. Groups potentially capable of transmitting influenza to high-risk persons should also be vaccinated.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Influenza surveillance.
The main objectives of influenza surveillance are: collection of influenza virus isolates and analysis of their antigenic characteristics so that the most appropriate virus variants can be recommended as constituents of influenza vaccines for use during the next epidemiological season; collection and analysis of information on influenza morbidity and mortality; and earliest possible detection of influenza epidemics. Exact estimates of the specific morbidity and mortality due to influenza are now being carried out in only certain countries. Simple notification of clinical cases and deaths without laboratory confirmation is unsatisfactory and leads to errors in interpretation. The methods used to predict baseline mortality may be inaccurate, resulting in underestimation of mortality associated with influenza virus infection. Comparison of the impact of influenza in different countries is also difficult owing to a variety of methods used for the estimation of mortality and morbidity. Although the laboratory aspects of influenza epidemiology are more uniformly covered worldwide than the statistical aspects, it is still necessary to increase laboratory coverage of some parts of the world and to improve the techniques for the isolation and characterization of not only influenza viruses but also other acute respiratory viruses. The systems and methods for influenza surveillance should be improved and standardized.
Epidemiologic Methods↗
WHO strategy for the global elimination of new cases of hepatitis B.
Hepatitis B infection and its sequelae remain major public health problems internationally despite the existence of sensitive tests to screen blood and blood products for hepatitis B surface antigen (HBsAg) and immunogenic vaccines. Since the human hepatitis B virus has no known animal reservoir, a systematic vaccination programme against hepatitis B, including vaccination of all newborns and young children within the framework of the WHO Expanded Programme on Immunization, as well as protection of high-risk individuals, together with the testing of all blood and blood products for HBsAg, could eliminate hepatitis B virus infection and its sequelae. However, for the successful realization of this programme, many important and difficult problems need to be solved, especially those related to vaccination strategy, determination of the duration of immunity, investigation of the mechanisms of perinatal and horizontal virus transmission, and improvement of the immunogenicity of hepatitis B vaccine. The problem of the hepatitis B carrier is also paramount as the eradication of hepatitis B can be achieved only after the 300 million carriers of the disease in the world today are either cured or dead.
Adolescent↗
The immune response to influenza vaccines.
Specific immunity to influenza is associated with a systemic immune response (serum haemagglutination inhibition antibody), local respiratory immune response (virus-specific local IgA and IgG antibodies in nasal wash), and with the cell-mediated immune response. Both inactivated and live influenza vaccines induce virus-specific serum antibody which can protect against infection with influenza virus possessing the same antigenic specificity. In the absence of serum antibodies, local antibodies in nasal wash are a major determinant of resistance to infection with influenza virus. In comparative studies in humans it was shown that nasal secretory IgA develops chiefly after immunization with live cold-adapted (CA) vaccine, but persistent nasal secretory IgG was detected in both CA live and inactivated vaccines. The origin of nasal wash haemagglutination inhibition (HI) antibodies is not completely known. Recently it was found that cytotoxic T-cells (CTL) play an important role in immunity against influenza and in clearance of influenza virus from the body. In primed humans, inactivated influenza vaccine stimulates a cross-reactive T-cell response, whereas the ability of inactivated vaccine to stimulate such immunity in unprimed humans has not been determined. Data on the T-cell response to live vaccine in humans are limited to the development of secondary T-cell responses in primed individuals vaccinated with a host-range (HR) attenuated vaccine. The data obtained have shown that immunity induced by inactivated influenza vaccines is presumably dependent on the stimulation of serum antibody. Live CA vaccines not only stimulate a durable serum antibody response, but also induce long-lasting local respiratory tract IgA antibody that plays an important role in host protection.
Antibodies, Viral↗
Vaccination against influenza viruses: current status.
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Antibodies, Viral↗
The immune response of humans to live and inactivated influenza vaccines.
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Humans↗
Perinatal transmission of hepatitis B virus in high-incidence countries.
Hepatitis B is a serious public health problem throughout the world. Hepatitis B virus (HBV) induces acute hepatitis with a case-fatality rate of about 1%. Even more important, 5-10% of patients infected with HBV become chronic carries and about 25% of these will die due to cirrhosis and hepatocellular carcinoma. The reservoir of HBV chronic carriers in the world is estimated at more than 200 million people and 80% of them reside in Asia and the western Pacific. In high-incidence areas, such as south-east Asia, perinatal transmission of HBV from carrier mothers to newborns appears to be the most important factor for the high prevalence of HBV infection and 70-90% of infants born to HBsAg/HBeAg-positive mothers become chronic carriers. Three possibilities of transmission of HBV from carrier mothers to newborns are suggested: (a) transplacental transmission in utero - it was estimated that such transmission occurred in 5-15% of newborns; (b) transmission during delivery, which is considered the main mode of perinatal transmission; (c) postnatal transmission from mother to newborn, which is not common. HBeAg is the main maternal factor in determining whether infection of newborns will occur; the expression of this antigen seems to be determined genetically. Recently it has shown that immunoprophylaxis is highly effective in preventing the development of the carrier state in infants born to HBsAg/HBeAg-positive mothers. Only 5-10% of high-risk infants are not protected by vaccination. If it becomes possible to immunize the entire world population including all babies born to carrier mothers at birth, and if our knowledge of the mechanisms of perinatal transmission of HBV is accurate, the carriers and acute cases of HB ought to disappear in two to three generations.
Asia, Southeastern↗
Haemagglutinin of influenza A virus is a target for the antiviral effect of Norakin.
The anticholinergic anti-parkinsonism drug Norakin is an inhibitor of influenza virus multiplication. By crossing a Norakin-resistant variant of fowl plague virus (FPV) strain Weybridge with the sensitive FPV/Rostock/34 wild-type virus, Norakin-resistant recombinants were obtained. Analyses of the gene composition showed that all Norakin-resistant recombinants had inherited their haemagglutinin gene from the Norakin-resistant parent strain. The majority of the recombinants had received all the other gene segments from the sensitive parent strain. Norakin was shown to inhibit red blood cell lysis induced either by purified virions or by the haemagglutinin of a sensitive FPV strain at low pH, but failed to affect the Norakin-resistant FPV variant. No aggregation of autoliposomes containing the haemagglutinin of a sensitive FPV strain or digestion of the HA1 subunit of haemagglutinin by trypsin occurred in the presence of Norakin at acid pH. The data suggest that the haemagglutinin of FPV is the target for the antiviral activity of Norakin, which acts by inhibiting the conformational change in the haemagglutinin at acid pH important for lysis.
Animals↗
The influence of Norakin on the reproduction of influenza A and B viruses.
The action of the anticholinergic drug Norakin (triperiden) on the reproduction of influenza virus A and B strains was studied. In cell culture, primary transcription of influenza A/FPV/Weybridge and of influenza B/Japan/73 is strongly inhibited by Norakin (20 micrograms/ml). When present simultaneously, Norakin and rimantadine exert an additive effect. Rimantadine-resistant mutants of influenza A exhibit a definite, though limited, cross-resistance to Norakin, and vice versa. The results indicate that Norakin blocks early stages of the infectious cycle and that the modes of antiviral action of Norakin and rimantadine are not identical.
Animals↗
Functional defects of fowl plague virus temperature-sensitive mutant having mutation in the neuraminidase.
A fowl plague virus (FPV) temperature-sensitive mutant ts 5 having mutation lesions in the gene coding for the neuraminidase has been obtained. The mutant induced synthesis of cRNA, vRNA and proteins in cells under non-permissive conditions, but formation of virions including non-infectious ones was defective. The neuraminidase and haemagglutinin synthesized under non-permissive conditions possessed functional activity and could migrate from the rough endoplasmic reticulum into plasma membranes; however, cleavage of the haemagglutinin was reduced. In ts 5-infected cells under non-permissive conditions the synthesis of segments 5 and 8 of cRNA and vRNA was predominant both early and late in the reproduction cycle, and the synthesis of P1, P2, P3, HA and M proteins was reduced after approximately 3 hours. The data obtained suggest that involvement of the neuraminidase in the formation of infectious virions may have no direct association with the enzymatic activity of this protein, and that the mutation in the neuraminidase may affect regulation of replication and transcription processes.
Cell Membrane↗
High reproduction capacity of recombinants between H3N2 human influenza and fowl plague viruses is due to the gene coding for M proteins.
Recombinants between H3N2 human influenza viruses (A/Victoria/3/75 and A/Bangkok/1/79, low-yielding parents in chick embryos) and fowl plague virus (FPV, a high-yielding parent in chick embryos) have been obtained. The high reproductive capacity of recombinants in chick embryos has been shown to be due to the gene coding for M proteins.
Animals↗
Extragenic suppression of a ts phenotype during recombination between ts mutants of two fowl plague virus strains with a ts mutation in gene 1.
Fowl plague virus (FPV) ts mutants belonging to six recombination groups and obtained from the Weybridge strain (in the U.S.S.R.) or the Rostock strain (in the U.K.) have been studied in a recombination test. Temperature-sensitive mutants obtained from different FPV strains were revealed which had a ts mutation in gene 1; however, their crossing resulted in ts+ recombinants which appeared with a high frequency. This phenomenon was due not to intragenic complementation but to extragenic suppression, when the expression of a ts phenotype of the Rostock strain mutant gene 1 is suppressed by gene 2 products of the Weybridge strain.
Gene Expression Regulation↗