Showing papers on "Influenza A virus published in 1977"

Generation of both cross-reactive and virus-specific T-cell populations after immunization with serologically distinct influenza A viruses.

Abstract: Specificity of cytotoxic T-cell function was investigated for a range of different influenza viruses T cells from mice immunized with A or B strain influenza viruses, or with vaccinia virus, showed reciprocal exclusion of cytotoxicity Extensive cross-reactivity was, however, found for lymphocyte populations from mice infected with a variety of serologically distinct influenza A viruses, though serum antibodies did not cross-react when tested in a radioimmunoassay using comparable target cells as immunoadsorbents This apparent lack of T-cell specificity was recognized for immune spleen cells generated after intraperitoneal inoculation of high titers of virus, and for mediastinal lymph node populations from mice with pneumonia due to infection with much less virus The phenomenon could not be explained on the basis of exposure to the chicken host component, which is common to A and B strain viruses However, not all of the virus-immune T-cell clones are cross-reactive Competitive-inhibition experiments indicate that a considerable proportion of the lymphocyte response is restricted to the immunizing virus Even so, the less specific component is significant Also, exposure to one type A virus was found to prime for an enhanced cell-mediated immunity response after challenge with a second, serologically different A strain virus

Inhibition of Influenza Virus Ribonucleic Acid Polymerase by Ribavirin Triphosphate

Abstract: Ribavirin 5′-triphosphate (RTP), derived from the broad-spectrum antiviral compound ribavirin (Virazole), can selectively inhibit influenza virus ribonucleic acid polymerase in a cell-free assay. Ribavirin and its 5′-monophosphate have no effect on the polymerase. The inhibition is competitive with respect to adenosine 5′-triphosphate and guanosine 5′-triphosphate. RTP also inhibits ApG- and GpC-stimulated influenza virus ribonucleic acid polymerase. Since ribavirin is phosphorylated in the cell, the inhibition of influenza multiplication in the cell may also be caused by RTP.

Virulence factors of influenza A viruses: WSN virus neuraminidase required for plaque production in MDBK cells.

Abstract: The genetic basis for the distinctive capacity of influenza A/WSN/33 (H0N1) virus (WSN virus) to produce plaques on bovine kidney (MDBK) cells was found to be related to virus neuraminidase. Recombinant viruses that derived only the neuraminidase of WSN virus were capable of producing plaques, whereas recombinant viruses identical to WSN except for neuraminidase did not produce plaques. With viruses that do not contain WSN neuraminidase, infectivity of virus yields from MDBK cells was increased approximately 1,000-fold after in vitro treatment with trypsin. In contrast, no significant increase in infectivity was observed after trypsin treatment of viruses containing WSN neuraminidase. In addition, polyacrylamide gel analysis of proteins of WSN virus obtained after infection of MDBK cells demonstrated that hemagglutinin was present in the cleaved form (HA1 + HA2), whereas only uncleaved hemagglutinin was obtained with a recombinant virus that derived all of its genes from WSN virus except its neuraminidase. These data are in accord with the hypothesis that neuraminidase may facilitate production of infectious particles by removing sialic acid residues and exposing appropriate cleavage sites on hemagglutinin.

Effects of Low- and High-Passage Influenza Virus Infection in Normal and Nude Mice

Abstract: A human isolate of type A Hong Kong influenza virus (H3N2) was adapted to mice by serial passage. Lung homogenates from mice who received low passage levels contained about the same quantity of virus (10(6.2-6.95) 50% tissue culture infective doses/ml) as those from mice who received high passage levels (10(5.95-6.45) 50% tissue culture infective doses/ml); however, death occurred only in animals given high-passage virus. Passage 3 (P3) and passage 9 (P9) viruses were selected as representative of low-passage and high-passage viruses, respectively. Although minimal differences were detected in infectivity for rhesus monkey kidney tissue cultures and mice, P9 virus was at least 10,000 times more lethal for mice (mean lethal dose = 10(4.2)). Infection with P3 virus was accompanied by minimal bronchitis and bronchiolitis only, whereas P9-infected animals exhibited marked bronchitis, bronchiolitis, and pneumonia. Striking thymic cortical atrophy was also demonstrable in the P9-infected animals and, although virus was more commonly recovered from thymuses from these animals, immunofluorescent studies revealed only a few cells containing influenza virus antigens. To further explore the participation of thymus-derived lymphocytes in influenza, athymic nude mice and furred immunocompetent littermates were given 500 50% mouse infectious doses of P9 virus. Nude mice exhibited an increased survival time and, in contrast to the extensive lung pathology seen in furred littermates, manifested minimal cellular infiltration and no tissue destruction in lungs. Brains from nude mice exhibited encephalomalacia with lymphocytic perivascular cuffing, which was not seen in furred animals. Virus was recovered from brains of 6 of 13 nude mice and 1 of 10 furred animals. The contrasting models suggest that thymus-dependent cells play a significant role in the inflammatory response to influenza virus infection and should prove useful for probing host-virus interactions which characterize influenza virus virulence.

Immunologic recognition of influenza virus-infected cells. II. Expression of influenza A matrix protein on the infected cell surface and its role in recognition by cross-reactive cytotoxic T cells

Abstract: Two distinct subpopulations of cytotoxic T cells are generated in the primary or secondary response of mice to type A influenza viruses. One subpopulation is specific for the immunizing virus strain. The other subpopulation shows a high degree of cross-reactivity for heterologous type A virus of a different subtype. This report examines the possibility that distinct influenza virus antigens, expressed on the surface of the infected cell, are recognized by the different subpopulations of influenza-specific cytotoxic T cells. Data are presented which demonstrate that influenza A matrix protein, an internal virion antigen, is detectable on the surface of target cells infected with influenza A viruses of different subtypes. Since this viral antigen is type specific, i.e., serologically cross-reactive among all type A influenza viruses, it could serve as the target for cross-reactive cytotoxic T cells. To further examine the specificity of the two cytotoxic T-cell subpopulations, experiments were carried out by using the inhibitor of glycoprotein synthesis - 2-Deoxy-D-Glucose 2-DG. These experiments examine first the effect of 2-DG on the expression of influenza matrix protein and viral glycoprotein on the infected cell surface and second, the susceptibility of 2-DG-treated target cells to lysis by cytotoxic T cells. 2-DG inhibits the expression of the viral hemagglutinin glycoprotein on the cell surface but does not inhibit the expression of the nonglycosylated matrix protein. Furthermore, inhibition of glycoprotein synthesis in infected target cells abrogates the reactivity of infected target cells to lysis by virus strain-specific but not cross- reactive cytotoxic T cells. These findings suggest that the influenza glycoproteins (hemagglutinin and/or neuraminidase) and the nonglycosylated matrix protein are the targets for the virus strain- specific and cross-reactive cytotoxic T cells, respectively. These results are discussed in the light of available information on influenza virus structure and the biology of influenza infection and in terms of current models for cytotoxic T-cell recognition of virus-infected cells.

Influenza immunization of adult patients with malignant diseases.

Abstract: To characterize the immunogenicity of influenza vaccine in patients with malignant disease, 21 patients with lymphoreticular neoplasms and 21 patients with solid tumors were immunized with inactivated influenza A/New Jersey/76 whole virus vaccine. The patients were randomized with respect to time of vaccine administration in relation to administration of chemotherapy. Fourfold or greater antibody titer increases occurred in 94% of controls and 71% of cancer patients (P less than 0.05), and the magnitude of antibody response was also significantly lower in cancer patients (P less than 0.01). There was no correlation of antibody responsiveness with sex, age, tumor type, absolute lymphocyte count, disease status, or type of chemotherapeutic agent used. Fifty percent of patients immunized at the time of chemotherapy administration showed seroconversion, which is significantly less than the 93% response rate observed in patients immunized between chemotherapy courses. It is thus recommended that individuals with malignant disease should receive influenza immunization between chemotherapy courses.

Influenza A infections in young children. Primary natural infection and protective efficacy of live-vaccine-induced or naturally acquired immunity

Abstract: To assess the impact of an influenza A/Port Chalmers infection on normal young children, we monitored 147 children during an epidemic; 121 were seronegative. There was a high attack rate (61 of 147), and a high rate of symptomatic disease (38 of 147), which resulted in frequent physician visits (25 of 38). Influenza accounted for 76 per cent of the sick-child visits during the two-month epidemic period. Young children undergoing primary influenza infection produced hemagglutination inhibition and antineuraminidase antibodies. Because of the immunologic responsiveness of young children, we examined the serologic correlates of protection. Ten children previously infected with influenza A/London and 16 who received live, attenuated A/Hong Kong ts-1[E] vaccine were protected against infection with the non-homologous A/Port Chalmers strain. The morbidity of influenza and ability of the young child to produce protective antibody should encourage evaluation of life, attenuated influenza vaccines in this age group.

Early presence of ribonucleoprotein antigen on surface of influenza virus-infected cells.

Abstract: HOST defence against influenza A virus in experimental animals seems to be mediated mainly by antibody1,2 The mechanism by which antibody protects the host, however, is unknown Antibody may either neutralise viral particles or recognise viral antigens at the surface of infected cells and then act at an early stage of infection, before viral replication is completed The latter mechanism is theoretically more efficient, but might cause immunopathological destruction of the infected cells with harmful consequences Viral envelope antigens (haemagglutinin and neuraminidase) have been shown to be present at the surface of influenza virus-infected cells, by haemadsorption3, electron microscopy4 and immunofluorescence5 Two main type-specific internal antigens have been described in influenza A virus—the matrix protein (MP) antigen6 and the ribonucleoprotein (NP) antigen7, a non-glycosylated polypeptide with a molecular weight of 58,000 (ref 8) Immunofluorescence studies on fixed cells have shown that NP antigen is first demonstrable in the cell nucleus and then appears as granular masses within the cytoplasm, which become prominent at the, cell borders later in infection, suggesting a close association with the cell membrane9 We report here that NP antigen can be detected by immunofluorescence as early as 2 h after the infection on the surface of unfixed mouse cells infected with influenza A virus

A perspective on the significance of pandemic influenza

Abstract: The identification in February 1976 of a new strain of influenza virus led to the enactment of unprecedented federal legislation to minimize the impact of a potential outbreak of pandemic influenza in the fall and winter of 1976-1977. This legislative program does not, however, represent a commitment of federal resources to deal with the more general, longstanding problem of epidemic influenza. This paper presents a series of estimates of the impact and economic consequences of influenza. By including periods of interpandemic as well as pandemic disease, the estimates offer a broadened perspective of the magnitude of the influenza problem. The estimates show that while the proportions of pandemic influenza can be singularly impressive, the cumulative effects of interpandemic outbreaks are generally of greater consequence. The paper discusses the implications of these estimates and the 1976 legislation for the support and implementation of federal policy on the use of influenza vaccine. While the commitment of resources in support of public policy cannot alone guarantee successful implementation, it must be considered an essential prerequisite for dealing with both interpandemic and pandemic influenza.

Suppression of cell-mediated immunity by street rabies virus.

Abstract: Mice lethally infected with street rabies virus failed to develop cytotoxic T cells specific for rabies virus-infected target cells, whereas high levels of cell-mediated cytotoxicity (CMC) were generated after nonfatal infection with the attenuated high egg passage (HEP) or ERA rabies virus strains. Furthermore concurrent infection with street, but not with HEP, rabies virus suppresses development of a primary (but not a secondary) CMC response specific for influenza virus. No cross-reactivity is found between effector T-cell populations from mice immunized with HEP or with influenza virus. It thus appears that street rabies virus, which is not known to replicate in the cells of immune system, induces some general defect in the primary CMC lymphocyte response, though restimulation of memory T-cell populations is unimpaired and there is no defect in antibody formation. Development of fatal rabies may reflect the operation of this selective immunosuppressive mechanism.

Potentiation of the Immune Response to Influenza Virus Subunit Vaccines

Abstract: Influenza subunit vaccines are poorly immunogenic in unprimed lower animals and man and methods were sought to potentiate the humoral response. Influenza B intact virus vaccines potentiated the antibody response of hamsters to purified vaccines containing influenza A hemagglutinin and neuraminidase subunits. The levels of antibody induced were at least as high as those induced by equivalent doses of whole virus. Similarly, intact heterologous influenza A virus vaccine (A/Victoria/3/75 [H3N2]) potentiated the antibody response of hamsters to A/NJ/76 [Hswl Nl] subunit vaccines but large doses of intact virus were required. Considerably lower doses of homologous intact A/NJ/76 [Hswl Nl] potentiated the antibody response of hamsters and sero-negative people to subunit vaccines. This suggests that future influenza subunit vaccines for use in seronegative people should contain a minimal dose of whole virus vaccine sufficient to potentiate the immune response to the subunits but insufficient to be reactogenic. A synthetic water soluble adjuvant ( N -acetyl-muramyl-L-alanyl-D-isoglutamine) was also shown to potentiate the immune response of hamsters to A/NJ/76 [Hswl Nl] influenza virus subunit vaccines.

Double-Blind Evaluation of Oral Ribavirin (Virazole) in Experimental Influenza A Virus Infection in Volunteers

Abstract: The prophylactic effectiveness of oral administration of ribavirin (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) against experimentally induced influenza A infection was evaluated in a double-blind clinical trial in normal volunteers. Fourteen men received ribavirin capsules (1,000 mg/day in four divided doses) and 15 other men received identical-appearing placebo capsules beginning 6 h after the intranasal inoculation of 3.4 log(10) 50% tissue culture infectious doses of influenza virus A/Victoria/3/75 H3N2 and continuing for 5 days after challenge. The total number of moderate-to-severe symptom scores and the total number of temperatures >/=100 degrees F (37.8 degrees C) were significantly lower in the ribavirin group compared with the placebo group. The mean quantity of virus shed in nasal wash specimens and the total number of days that there were viral titers greater than 1.0 log(10) 50% tissue culture infectious doses per ml were significantly greater in the placebo group. There was no difference between the frequencies of virus isolated or the antibody responses in the two groups. Therefore, prophylactic ribavirin ameliorated symptoms and fever indicative of moderate-to-severe illness, but had no effect on the manifestations of mild illness in response to influenza A challenge. A transient rise in total serum bilirubin occurred in 29% of the ribavirin-treated volunteers and in none of the placebo-treated volunteers.

Synthesis of influenza virus polypeptides in cells resistant to alpha-amanitin: evidence for the involvement of cellular RNA polymerase II in virus replication.

Abstract: Influenza virus polypeptides were not synthesized in wild-type CHO-S-infected cells in the presence of alpha-amanitin, but were synthesized in CHO-Amal cells, a mutant cell line whose DNA-dependent RNA polymerase II is specifically resistant to this drug, indicating that this cellular enzyme is involved in influenza virus replication. The results of experiments designed to detect viral polypeptides synthesized from primary transcripts suggest that the synthesis of a cellular RNA species by RNA polymerase II is required for primary transcription of the influenza virus genome.

Immunity to attenuated influenza virus WRL 105 infection induced by heterologous, inactivated influenza A virus vaccines.

Abstract: Groups of student volunteers were immunized with one of five different inactivated influenza virus vaccines. The concentration of virus in the various vaccines differed by both the international unitage test and by the concentration of haemagglutinin, as measured by the single radial diffusion test; the results of the two methods of standardization showed no correlation. The serum HI response to immunization was variable; volunteers given A/England/72 showed a 16.6-fold increase in homologous serum antibody titre whilst volunteers given A/Hong Kong/68 vaccine showed a 4.2-fold increase. The variable response of volunteers to immunization could not be explained by the varied concentration of virus in the vaccines, as measured by either test, the titres of serum HI antibody present before immunization, or a combination of these two factors.The ability to infect volunteers with WRL 105 virus 4 weeks after immunization with heterologous, inactivated virus vaccine was directly related to the degree of cross-reactivity between the haemagglutinins of this vaccine virus and WRL 105 virus. Thus, the greatest number of infections by the challenge virus were seen in volunteers given A/Hong Kong/68 vaccine, less were observed in volunteers given A/England/72 vaccine, and least were found in groups given A/Port Chalmers/73 or A/Scotland/74 vaccine. However, compared with the incidence of infection in volunteers given B/Hong Kong/73 vaccine, all the heterologous influenza A vaccine gave some immunity to challenge infection.

Hemagglutinin-specific cytotoxic T-cell response during influenza infection.

Abstract: Specific cytotoxic thymus-derived (T) lymphocytes were detected in the cervical lymph nodes and spleen during influenza infection of mice. The cytotoxic T cells can distinguish target cells infected with different influenza A subtypes. Infection with parent viruses and their recombinant progeny possessing the hemagglutinin of one parent and the neuraminidase of the other demonstrated that significant cytotoxicity occurred only when the hemagglutinin of the immunizing viruses was the same as that of the virus used to infect the target cell. In addition to this specific cytotoxic response to the major surface antigen, a cross-reactive response could be detected when the relatively nonpermissive L cell was used as the target cell. These results indicate there is a specific cytotoxic T-cell response to the surface hemagglutinin, and a cross-reactive cytotoxic response, not directed to the hemagglutinin, during influenza infection. The cytotoxic T-cell response specific for the hemagglutinin antigen may play an important role in in vivo immunity to influenza.

Maintenance of viability and comparison of identification methods for influenza and other respiratory viruses of humans.

Abstract: A comparison of Hanks balanced salt solution, veal infusion broth (VIB), and charcoal viral transport medium for maintaining viability of type A influenza virus indicated approximately equal survival of virus on all three media at -70 and 4 degrees C, whereas at 25 degrees C virus survived best in VIB VIB supplemented with bovine serum albumin was used as transport medium in a community-wide surveillance of febrile respiratory disease for influenza viruses Unfrozen throat swab specimens were placed in VIB and stored at 4 degrees C for up to 5 days without effect on isolation frequencies of either type A or type B influenza virus or type 1 or type 3 parainfluenza virus Comparison of indirect immunofluorescence with hemadsorption for detection of type A influenza virus in rhesus monkey kidney cultures revealed a requirement for at least five fluorescing cells to eliminate false positive indirect immunofluorescence tests and at least 3 days of incubation to eliminate false negative tests when compared with hemadsorption at later times Detection frequencies for the two methods after 2 and 3 days of incubation were not significantly different

Clinical and Immunologic Evaluation of NeuraminidaseSpecific Influenza A Virus Vaccine in Humans

Abstract: Groups of schoolchildren were immunized with an inactivated recombinant influenza virus vaccine specific for the neuraminidase antigen of Port Chalmers influenza A virus (Heq1N2Ch), a conventional biphasic Port Chalmers strain of influenza virus vaccine (H3ChN2Ch), or a placebo. Immunization with either virus vaccine was found to be safe and had no major adverse effects. Immunization with the Heq1N2Ch vaccine resulted in no specific hemagglutination-inhibiting antibody response to H3Ch antigen, although a specific neuraminidase antibody response to N2Ch antigen was observed in greater than 90% of the vaccinees. A subsequent natural outbreak of influenza virus resulted in serologically proven infection with H3Ch virus in 26% of vaccinees receiving H3ChN2Ch virus vaccine, 47% of those receiving Heq1N2Ch virus vaccine, and 44% of those receiving a placebo. However, the protective efficacy against illness was 74.3% for the H3ChN2Ch vaccine and only 51.4% for the Heq1N2Ch vaccine. Regardless of the type of vaccine employed, vaccinees with serologic evidence of infection and clinical illness were found to have very low titers of hemagglutination-inhibiting and neuraminidase antibody. However, vaccinees with serologically proved infection but without clinical illness were found to have titers of antibody to neuraminidase before infection that were four- to eightfold higher than titers in vaccinees who were infected and who had clinical illness.

Identification and Preliminary Antigenic Analysis of Swine Influenza-Like Viruses Isolated during an Influenza Outbreak at Fort Dix, New Jersey

Abstract: The sequence of events and the laboratory procedures that resulted in the identification of swine influenza-like viruses isolated during an influenza outbreak at Fort Dix, New Jersey in January and February of 1976 are described. Preliminary antigenic analysis suggested that the isolates from Fort Dix are closely related to a 1975 isolate of swine influenza virus and distinguishable from earlier swine influenza strains.

Potentiation of the immune response to influenza virus subunit vaccines.

Abstract: Influenza subunit vaccines are poorly immunogenic in unprimed lower animals and man and a method was sought to potentiate the humoral response. Intact heterologous influenza A virus vaccine (A/Victoria/3/75 [H3N2]) potentiated the antibody response of hamsters to A/NJ/76 [Hsw1 N1] subunit vaccines but large doses of intact virus were required. Studies in seronegative young human adults showed that much lower doses of homologous A/NJ/76 [Hsw1 N1] virus potentiated the antibody response to both the hemagglutinin and neuraminidase subunits of A/NJ/76 influenza vaccines. This suggests that future influenza subunit vaccines for use in seronegative people should contain a small amount of whole virus vaccine, sufficient to potentiate the immune response to the subunits but insufficient to be reactogenic.

Structural components of influenza C virions.

Abstract: The genome RNA species of influenza type C virions were analyzed by polyacrylamide gel electrophoresis. The pattern obtained was found to resemble those of other influenza viruses. Six RNA species were resolved, with estimated sizes ranging from 0.37 X 10(6) to 1.25 X 10(6) daltons. The internal ribonucleoproteins of influenza C virions were found to sediment heterogeneously in glycerol velocity gradients as demonstrated previously with influenza A/WSN virus. The ribonucleoproteins possessed diameters of 12 to 15 nm, with lengths ranging from 30 to 100 nm. Of the three major virion polypeptides (molecular weights, 88,000, 66,000, and 26,000), only the largest is glycosylated. Similar polypeptide species were present in influenza C virions of five different strains. All three major proteins of influenza C virions possess electrophoretic mobilities distinguishable from those of the major polypeptides of influenza A/WSN. The 66,000-dalton protein is associated with the ribonucleoprotein components. Two additional glycosylated polypeptides, with estimated molecular weights of 65,000 and 30,000, were detected in virions grown in embryonated eggs, but not in virus particles obtained from chicken embryo fibroblasts.

Identification of the defective genes in three mutant groups of influenza virus.

Abstract: Seven complementation-recombination groups of temperature-sensitive (ts) influenza WSN virus mutants have been previously isolated. Recently two of these groups (IV and VI) were shown to possess defects in the neuraminidase and the hemagglutinin gene, respectively, and two groups (I and III) were reported to have defects in the P3 and P1 proteins which are required for complementary RNA synthesis. In this communication we report on the defects in the remaining three mutant groups. Wild-type (ts+) recombinants derived from ts mutants and different non-ts influenza viruses were analyzed on RNA polyacrylamide gels. This technique permitted the identification of the P2 protein, the nucleoprotein, and the M protein as the defective gene products in mutant groups II, V, and VII, respectively. Based on the physiological behavior of mutants in groups II and V, it appears that P2 protein and nucleoprotein are required for virion RNA synthesis during influenza virus replication.

Cell-mediated immune responses in humans after induced infection with influenza A virus.

Abstract: Cell-mediated immune responses were examined in 19 normal volunteers after intranasal administration of three strains of influenza A virus. Eight volunteers manifested respiratory tract illness along with fourfold rises of serum antibody and/or virus shedding. Samples of peripheral venous blood were obtained before and two days, five days, and four weeks after challenge. During acute illness, infected volunteers showed lymphopenia, which persisted for up to four weeks after challenge. The lymphopenia involved thymus-derived, bone marrow-derived, and null cells. Blastogenic responses of lymphocytes to stimulation with phytohemagglutinin, concanavalin A, and streptokinase-streptodornase were depressed during acute illness, and responses to phytohemagglutinin and concanavalin A remained depressed at four weeks after infection. Thus, influenza infection in humans can result in prolonged depression of numbers and functions of circulating lymphocytes.

Reactogenicity and immunogenicity of bivalent influenza A and monovalent influenza B virus vaccines in high-risk children.

Abstract: Seventy-nine high-risk children were immunized with either commercial, bivalent, split-product influenza A vaccine or purified hemagglutinin-neuraminidase bivalent influenza A vaccine, and 78 of these subjects were immunized with commercial, monovalent, influenza B split-product vaccine. The reactogenicity of all three vaccines was low, and there were no severe reactions. Twenty-nine subjects who received hemagglutinin-neuraminidase vaccine as their initial dose and commercial split-product vaccine as a booster dose had significantly lower antibody responses to influenza A/New Jersey/76 virus than subjects who received two doses of commercial split-product vaccine. The responses of the two groups to influenza A/Victoria/75 virus were comparable. Twenty-four subjects with malignancy who were receiving chemotherapy were compared with a group of subjects matched for age and vaccine preparation. Patients with cancer had significantly lower antibody responses to A/New Jersey/76 virus than patients without cancer. The ultimate responses of patients with cancer to A/Victoria/75 and B/Hong Kong/72 viruses were comparable to those of other patients, but early responses were lower.

Matrix protein from influenza A virus and its role in cross-protection in mice.

Abstract: The matrix (M) protein of influenza A virus, one of the two group-specific internal proteins of the virion, was isolated in a pure form, and its immunogenicity was stable to heating at 100 degrees C for 2 min. Mice immunized with isolated M protein in complete Freund adjuvant and subsequently infected with influenza virus cleared virus more rapidly from their lungs than did unimmunized mice. Despite the rapid clearance of virus, the mice developed pneumonia that was at least as severe as in unimmunized mice. Preliminary studies suggest that the rapid clearance of influenza virus from the lungs of mice immunized with M protein may be initiated by a cell-mediated rather than a humoral response. The mechanism by which a cross-reactive internal virion protein can initiate clearance of the different subtypes of influenza is not clear. Perhaps the M protein is exposed on the surface of the virus-infected cell and is responsible for the cross-reactivity at the cytotoxic T-cell level recently detected between influenza A virus subtypes.

Reaction of Squirrel Monkeys to Intratracheal Inoculation with Influenza/A/New Jersey/76 (Swine) Virus.

Abstract: To determine whether a model could be established for laboratory investigations, nine squirrel monkeys were inoculated intratracheally with 10(7) median egg-infectious doses of influenza virus type A/New Jersey/8/76 (HSW1N1) (swine influenza virus). They responded with clinically detectable illness including fever, leukopenia, decreased food consumption, increased respiratory rate, occasional coughing, labored breathing, nasal discharge, and lethargy. Convalescence was well advanced by the day 10. All monkeys excreted virus for 7 to 8 days. A scoring procedure (illness score) has been developed for use in studies of vaccine and chemotherapeutic efficacy.

Influenza subunit vaccine: antibody responses to one and two doses of vaccine and length of response, with particular reference to the elderly.

Abstract: Antibody responses to subunit influenza vaccine prepared against A2/England/42/72 (h3n2) were studied in 69 volunteers aged 60 and over and 231 aged 59 and below over 12 months in 1973 and 1974. After two doses of vaccine seroconversion frequencies and geometric mean haemagglutination-inhibition (HI) titres were higher in the elderly, but no differences were observed between the two groups in the length of their responses. Sixteen (23%) of the elderly volunteers seroconverted only after receiving a second dose of vaccine or seroconverted twice after receiving both doses of vaccine. It was considered justifiable, therefore, to recommend the continuation of a two-dose schedule for patients in a high-risk category. Within 30 weeks of vaccination 87 (29%) volunteers had considerably reduced HI titres (less than 48), which might indicate potential susceptibility to influenza during an epidemic, and the number had risen to 132 (44%) by 50 weeks. It was suggested that high-risk patients should receive annnual vaccination two to four months before the possible epidemic period.