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PubMed1999

Difficulties in standardizing the neuraminidase content of influenza vaccines.

To achieve better standardization of influenza vaccines, an ELISA immunocapture assay was developed for N2 neuraminidase quantification. This sensitive and highly specific assay was successfully applied to vaccine preparations produced in embryonated hens' eggs from 1992 to 1997 and to antigenically related viral suspensions produced in MDCK cells. A study of the neuraminidase activity of prototype A/H3N2 strains stored at 4 degrees C showed the gradual development of enzymatic instability from 1994 onwards, accompanied by antigenic modifications of the antigen. As the phenomenon was also more pronounced with the recombinant, the question arose of the standard of immunity provided when such viruses are used for vaccination. The antibodies inhibiting neuraminidase activity in vaccinated subjects were monitored in parallel using both complete virus and purified N2 NA. The study revealed the existence of an interference phenomenon which resulted in the titre of the N1 antibodies being overestimated. The interference was due to anti-HA antibodies impeding access to the substrate at the enzymatic site by steric hindrance.

Animals↗

PubMed1976

Immunotherapy with neuraminidase-treated cells and bacillus Calmette-Guerin.

Experiments were designed to determine the effectiveness of active immunotherapy, both specific (neuraminidase-treated cells) and nonspecific [bacillus Calmette-Guerin (BCG) organisms] in the L1210-BDF1 tumor-host system. Tumor burden was minimized with chemotherapy (1,3-bis-(20chloroethyl)-1-nitrosourea) prior to immunotherapy. The effectiveness of immunotherapy was dependent on the amount of drug used to minimize tumor burden. An interval 36 hours between chemotherapy and immunotherapy produced the maximum number of survivors. A single immunization with 10(4) neuraminidase-treated cells was superior to other single or multiple immunizations. BCG was most effective when mice were given 393 X 10(5) organisms. Beneficial effects of immunotherapy were observed only when immunizations were given by an intraperitoneal route. All mice cured of tumor developed tumor-specific immunity. The highest levels of immunity were observed in mice given both neuraminidase-treated cells and BCG organisms after chemotherapy.

Animals↗

PubMedDate not supplied

[Serological study of the neuraminidase activity of cholera filtrate and influenza virus].

The capacity of homologous (influenza virus) and heterologous (V. cholerae) anti-neuraminidase antibody to neutralize the neuraminidase activity of influenza virus was studied. The lack of antigenic relationship between the enzyme of V. cholerae and that of influenza virus was established and differences in the antigenic structure of neuraminidase of influenza virus of both different types (A0, A1, A2) and within one type were demonstrated.

Animals↗

PubMed2000

[Neuraminidase inhibitors in therapy of influenza].

Neuraminidase promotes influenza virus release from infected cells and facilitates virus spread within the respiratory tract. Several specific inhibitors of these enzyme have been developed. Zanamivir and oseltamivir are the nowadays available neuraminidase inhibitors. In contrast to amantadine and rimantadine, which target the M2 protein of influenza A, they inhibit the replication of both influenza A and B. Zanamivir is delivered by inhalation because of its low oral bioavailability. Oseltamivir can be administered orally. Early treatment reduces the severity and duration of illness and associated complications. These drugs are not effective at afebrile, mild courses, or if the influenza symptoms have existed already for more than 2 days. They are not effective against other respiratory viruses. For an optimal usage of the neuraminidase inhibitors a rapid and reliable diagnosis is necessary. The clinical diagnosis is sufficient only in proven epidemics. An increased availability of sensitive and specifically diagnostical tests is necessary for individual therapy decisions. The influenza vaccination is the most effective measure against influenza.

Antiviral Agents↗

PubMed1975

Effect of neuraminidase on potency of inactivated influenza virus vaccines in mice.

The protective effect of neuraminidase was studied in a mouse protection test using isolated neuraminidase of A2/Aichi/68(H3N2) virus and the complete recombinant virus A/eq(Heq-1)-HK(N2) as antigens. Immunized mice were protected against A2/Aichi(H3N2) challenge virus; however, the protection rate was low in comparison to animals immunized with comparable amounts of the complete A2/68(H3N2) virus9 Furthermore there was no cross-protection against A2/Asia/57(H2N2) challenge virus. The protective effect of neuraminidase was not impaired by Tween-ether treatment of the A/eq(Heq-1)-HK(N2) recombinant virus.

Animals↗

PubMedDate not supplied

[Analysis of toxin genetic determinants of Vibrio cholerae virulence cassette and neuraminidase with DNA probes].

V. cholerae strains of different origin have been studied for the presence of cholera toxin genes (vct), the proximal part of the virulence cassette including genes zot, ace and orfU, as well as neuraminidase genes (neu), in their genomes with the use of molecular DNA probes. The possibility, in principle, for some strains to lose only a part of their virulence cassette (gene vct), while retaining its proximal part has been shown. In most cases such strains are isolated from patients with diarrhea of different severity and may probably play some etiological role, provided that the expression of the genes of additional toxins of the virulence cassette occurs. The gene expressing neuraminidase which facilitates the penetration of cholera toxin into the epithelial cells of the intestine is always present in vct+ strains and may be absent in vct- strains. The absence of genetic relationship between neuraminidases in V. cholerae O139 and V. cholerae O1 and non-O1 (non-O139) has been confirmed. The problems in connection with the integration and deletion of genetic determinants of V. cholerae virulence factors are discussed.

Cholera Toxin↗

PubMed2001

Synthesis of influenza neuraminidase inhibitors.

Influenza neuraminidase inhibitors provide a means to combat flu, a potentially very serious disease. For the first time, there is a way to treat influenza by blocking the influenza enzyme neuraminidase to stop or slow the progression of infection. The diverse structures and synthesis of several influenza neuraminidase inhibitors are discussed. Contributions from chemical process development groups are highlighted for those compounds that have reached the market, such as zanamivir and oseltamivir phosphate.

Antiviral Agents↗

PubMed1975

Selective chemical changes of gonadotropic hormones by means of neuraminidase from Vibrio cholerae.

Experiments indicate that Neuraminidase from Vibrio Cholerae selectively cleaves sialic acid derivate from FSH, but leaves the LH sialic acid derivative. By performing a specific test for LH - the OAAD test - we found that the LH activity is not influenced by the presence of Neuraminidase. The FSH activity is destroyed by Neuraminidase but the enzyme itself influences the ovarian weight, resulting in a weight decrease observed 48 hours after injection. Before or after this "critical time" no decrease is observed.

Animals↗

PubMed1976

[Reduction of the biological activity of Vibrio cholerae culture filtrates exposed to neuraminidase inhibitors].

Experiments were conducted on a model of edema of albino mouse paws; a study was made of the effect of neuraminidase inhibitors on the cholerogenic effect of a filtrate of cholera vibrio culture. It appeared that addition to the filtrate of inhibitors depressed its biological activity. Since no cholerogenic action was possessed by the purified neuraminidase preparations from the cholera vibrios it was suggested that there existed a chemical affinity between the region of cholerogen responsible for fixation on the cell membranes and the active neuraminidase centre.

Animals↗

PubMed1976

The migration of lymphocytes across specialized vascular endothelium. II. The contrasting consequences of treating lymphocytes with tryspin or neuraminidase.

Lymphocytes were exposed in vitro to either trypsin or neuraminidase. The ability of the treated cells to migrate into tissues were measured (a) by i.v. injection into intact recipients and (b) by vascular perfusion through an isolated lymph-node preparation. The localization of trypsinized cells in the lymph-nodes of recipients was deficient when compared to untreated lymphocytes and there was a surplus of trypsinized cells in blood. Trypsinized cells migrated into the isolated nodes in reduced numbers. By contrast, neuraminidase treated lymphocytes were markedly deficient in the blood of recipients early after injection; their localization in the spleen and lymph-nodes was also deficient but they were in surplus in the liver. Moreover they migrated into the isolated nodes in slightly increased numbers. By 24 hr after injection the perturbed localization pattern produced by either enzyme was partly restored to normal. In conclusion, tryspin interfered with the capacity of lymphocytes to migrate into lymph-nodes but neuraminidase did not; the latter promoted the hepatic sequestration of cells and the reduced localization in the blood and tissues was a consequence of this. The hypothesis that lymphocytes adhere to specialized endothelia in lymph-nodes because of specific glycoside sequences on their surface lacks experimental support.

Animals↗

PubMed2003

Review of the use of neuraminidase inhibitors for prophylaxis of influenza.

Influenza causes significant morbidity and mortality particularly in vulnerable population groups. Although vaccination is recommended as the primary method of preventing influenza, antiviral drugs may play a complementary role. The National Institute for Clinical Effectiveness (NICE) has recently published guidance on the use of anti-viral drugs in the treatment of influenza, and further guidance on their use for prophylaxis is expected later in the year. In anticipation of this guidance this paper reviews the evidence for the effectiveness of the prophylactic use of neuraminidase inhibitors. Results of this review show that neuraminidase inhibitors are effective in preventing laboratory-confirmed clinical influenza in healthy adults, both when used as post-exposure prophylaxis for close and household contacts, and as seasonal prophylaxis in the wider community. Direct evidence in the elderly and institutions is too limited to draw firm conclusions about their effectiveness in that setting. However it seems probable that neuraminidase inhibitors would also be effective in these groups.

Acetamides↗

PubMedDate not supplied

[Presence of neuraminidase in Rhodnius prolixus infected with Trypanosoma rangeli].

Using three different methods, the activity of neuraminidase was studied in the promesenteron, postmesenteron, rectal ampulla, haemolymph and salivary glands in 600 Rhodnius prolixus experimentally infected with Trypanosoma rangeli stock San Agustín. The haemagglutination method with peanut lectin, and the fluorescence test with peanut lectin conjugated with fluorescein isothiocyanate, and the fluorescence emitted by 4-methylumbelliferone showed in all cases the presence of neuraminidase in the supernatant culture of T. rangeli in Tobie's medium between 8 to 15 days growth. None of the three methods was able to detect the presence of neuraminidase in R. prolixus infected with T. Rangeli, thus suggesting that this enzyme is not produced in vivo, and consecutively is not implicated in the pathogenicity that this trypanosome has to its vector.

Animals↗

PubMed2003

[Neuraminidase inhibitor, anti-influenzal agent--mechanism of action, and how to use clinically].

Neuraminidase inhibitor has changed the treatment of influenza dramatically. The drug is effective for both influenza A and B whereas amantadine, another anti-influenzal agent, inhibits influenza A virus infection but not B. Neuraminidase inhibitor blocks the process of release of influenza virus from infected cells and inhibit the virus transmission to the neighboring cells. Neuraminidase inhibitor improves the symptoms of influenza and shortens the duration of illness. It is emphasized that this drug should be given within forty-eight hours after the onset, and it must be not noted that the possibility of the drug resistant virus although it is observed infrequently. Prophylactic use of the drug is also discussed.

Acetamides↗

PubMed2004

[Neuraminidase inhibitors oseltamivir and zanamivir: new means of defence against influenza].

Recently two new neuraminidase inhibitors zanamivir and oseltamivir have been marketed. They appear to considerably reduce morbidity and mortality from influenza. Their adverse effects are infrequent and mild and the chance of development of pathogenically significant resistant mutants appears to be small. During the first six months of a pandemic, neuraminidase inhibitors are the only defence against the virus. It is therefore important to stockpile in each country sufficient quantities of these drugs. During the usual influenza epidemics the main value of neuraminidase inhibitors lies in their use for therapy, prophylaxis and post-exposure prophylaxis in long-term care institutions for the elderly (for prophylaxis only oseltamivir is licensed). Although data on the effectiveness against complications of influenza and on the effect on people with an increased risk of (fatal) complications as a result of an influenza virus infection are limited, the available information on the effects of the neuraminidinase inhibitors indicates that these drugs will also protect against complications and that high-risk groups will benefit from the rapid deployment of these products. The cost-effectiveness of treatment and post-exposure prophylaxis with neuraminidinase inhibitors is probably not favourable for healthy children and adults but seems to be favourable for the high-risk groups (vaccinated or not) in winter.

Acetamides↗

PubMed1992

[Neuraminidase activity in representatives of the genus Francisella].

In two Francisella species (F. tularensis and F. novicida) neuraminidase activity, heretofore unknown, was detected. The enzyme exhibited specificity with respect to the substrates used in the investigation, neutralizing natural mucins, but not other compounds (glycoproteins and glycoproteins). All F. tularensis strains were found to have enzymatic activity irrespective of their subspecies, but neuraminidase activity was higher in the strains belonging to the American subspecies. Experimentally obtained F. tularensis noncapsular variants possessed higher neuraminidase activity than the capsular parent strains. The conclusion on the possible role of this enzyme in F. tularensis colonization of the host body was made.

Bacterial Capsules↗

PubMed1992

Dermatonecrotic lesions in rabbits caused by neuraminidase.

In an attempt to study the role of neuraminidase in cholera vibrio pathogenesis, the dermatonecrotic effect of a purified neuraminidase preparation was studied in rabbits. The experiments demonstrated that dermatonecrotic lesions resulted from intracutaneous injection of a purified neuraminidase preparation (0.5 specific human dose or 1 NU) as well as significant doses of cholera toxoid containing the enzyme (4,12,18 specific human doses).

Animals↗

PubMed2003

Neuraminidase assays.

Anti-neuraminidase (NA) antibodies (Ab) play a role in protection against influenza and in combination with anti-HA Ab they increase the protection in mice. To control the NA content of vaccines, which should improve vaccine standardisation and may benefit vaccine efficacy, a series of questions must be addressed: 1) The antigenic characterization of NA in vaccine strains and seed lots is based on the measurement of the enzymatic (E) activity using fetuin as substrate. The antigenic profile is established by inhibiting the E activity with post infectious ferret antisera. Overnight incubation ensures sensitivity, and fetuin substrate gives specificity by detection of variant specific antibodies. Several difficulties have to be overcome, such as the low level of E activity in MDCK grown viruses, and the lability of N1. 2) The NA protein content of the vaccines (in bulk or final product) can be measured by an ELISA capture test but the lability of the NA proteins at 4 degrees C must be checked. 3) The anti NA Ab response can be measured using a neuraminidase inhibition test. --The steric hindrance by HI antibodies does not exceed a titre of 20 in human sera. --Triton treatment of viruses reduces the steric hindrance in polyclonal sera and monoclonal antibodies but unmasks epitopes. 4) The correlations between neuraminidase inhibition, neutralization and protection, has been established in the mouse model, but remains to be shown in humans. 5) The use of a small fluorescent (MUN) or chemiluminescent (NA-STAR) substrate can be used for the rapid differentiation of N1 from N2 and NB, but not for the titration of protective NI antibodies.

Animals↗

PubMed1990

Studies on adaptation of influenza virus replicated at low temperature.IV. Sensitivity of neuraminidase and hemagglutinin to some proteolytic enzymes, detergents and chemical agents.

Resistance against proteolysis enzymes, detergents and chemical group-specific reagents has been compared for the neuraminidase and hemagglutinin of influenza virus replicated at low temperature and original strain replicated at 37 degrees C before and after passage in the susceptible animal organism - cotton rat. Our study indicated great differences between strains and temperature conditions to resistance of the neuraminidase and hemaglutinin to proteolytic enzymes, detergens and chemical group specific reagents. No differences was found for sensitivity of influenza virus replicated at low temperature before and after passages for 3 strains -A/Pol/L/71, A/Phil/2/82, A/Pol/79/85 which are really cold adapted viruses. On the other hand neuraminidase of this strains was more resistance to these treatments.

Adaptation, Physiological↗