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PubMed1977

Influenza in New Jersey in 1976: isolations of influenza A/New Jersey/76 virus at Fort Dix.

An outbreak of febrile respiratory disease at Fort Dix, New Jersey, beginning in January 1976, yielded five isolates of influenza A/New Jersey/76 virus and 42 isolates of strains resembling influenza A/Victoria/75 virus. Despite extraordinary efforts and the study of 305 verified cases of infection with type A influenza virus throughout the region, no additional instances of infections with influenza A/New Jersey virus were detected in humans.

Humans↗

PubMed1977

Identification and preliminary antigenic analysis of swine influenza-like viruses isolated during an influenza outbreak at Fort Dix, New Jersey.

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.

Antigens, Viral↗

PubMed1977

Antibody to influenza virus matrix protein detects a common antigen on the surface of cells infected with type A influenza viruses.

Antisera to the type-specific internal influenza virus matrix (M) protein of a type A influenza virus were produced in goats. In the presence of complement, anti-M serum was cytotoxic for target cells which were infected with a variety of serologically distinct type A influenza viruses, but did not react with type B influenza virus-infected cells. Absorption experiments indicated that anti-M serum detected a common antigen(s) on the surface of type A-infected cells. This serological cross-reactivity parallels the cross-reactivity observed for the cytotoxic T-cell response to type A viruses.

Antibodies, Viral↗

PubMed1976

Amantadine effect on peripheral airways abnormalities in influenza. A study in 15 students with natural influenza A infection.

Amantadine HCl administration has resulted in accelerated resolution of influenza A illness. Prolonged abnormalities in pulmonary function have been described in uncomplicated influenza A. To study the effect of amantadine on these changes, we evaluated young adults with documented natural influenza A with clear chest examinations and X rays. Subjects received placebo or amantadine in random, double-blind fashion. Physiologic studies included maximal expiratory flow volume curves with air and helium-oxygen mixtures. Air flow rates were unchanged in all subjects throughout. Initially, both groups showed comparable decreases in mean helium-oxygen maximal expiratory flow rates. The amantadine group showed accelerated physiologic improvement: significant increase in helium-oxygen flow rates occurred within 7 days (P less than 0.05). The rate of improvement in the helium-oxygen flow rates in the placebo group was not statistically significant. These studies confirm peripheral airways dysfunction after uncomplicated influenza A and suggest that amantadine is associated with accelerated resolution of this dysfunction.

Adult↗

PubMed1975

Toxicities of influenza vaccine: peripheral leukocytic response to live and inactivated influenza viruses in mice.

Intraperitoneal or intravenous inoculation of live or inactivated influenza virus induced two characteristic responses of the peripheral leukocytes in mice, an early appearing leukopenic response and late appearing lymphopenia. The former response usually developed and subsided within several hours, though the change in leukocyte population was fairly complicated depending upon the activity of the inoculated material, while the latter began several hours after inoculation and reached its minimum level in 10 to 20 hr. The agent responsible for the former may be virus pyrogen, while the latter seems to be caused by some substance(s) other than that. The early appearing leukopenic response was similar to that due to bacterial endotoxin in respect to the characteristic pattern of the change in peripheral leukocyte population, though it was relatively easy to distinguish one from the other by the length of the latent period and by the heat stability of the causative agent. Live or inactivated influenza virus causing the early appearing leukopenic response was found also to have the mouse body weight-decreasing toxicity. The significance of these findings in the laboratory control test of influenza vaccine for untoward reactions often observed in human inoculated with some inactivated influenza vaccines was discussed. The possible roles of the two agents, virus pyrogen and endotoxin, in the febrile response were mentioned.

Animals↗

PubMedDate not supplied

[Dynamics of antihemagglutinine (inhibitors and antibodies) to influenza virus in children with acute leukemia concurrently with influenza].

The study on the dynamics of some aspects of humoral immunity to influenza in children with acute leukosis in the presence of intercurrent influenza infection revealed two kinds of changes: a decline of a comparatively high initial level of antibody and inhibitors, and a rise in their titres when the initial level was lower. Both kinds of changes are characteristic both of the acute stage and the remission of acute leukosis. The chemotherapeutic treatment exerted no visible effect either on the level of the dynamics curve or on the pattern of serological shifts after influenza infection. These results suggest that in children with acute leukosis the response to influenza infection, being no different in nature from that in subjects not suffering from leukosis, is still poor quantitatively.

Acute Disease↗

PubMed1976

Swine influenza virus and the recycling of influenza-A viruses in man.

Sera collected in 1967 and 1972 from people in the 0-100 age-group showed haemagglutination-inhibition (H.I.) antibody to swine virus A/Iowa/15/30 (Hsw1N1) in greatest number and with highest titre in people born before 1918. A slight decrease was observed from 1967 to 1972 in the number of sera with antibody to swine virus and in the height of the titres. The recently isolated A/New Jersey/10/76 (Hsw1N1) virus showed a result comparable to that of the Swine/1930 virus in sera of 1972. On the analogy of the findings in 1968, when the Hong Kong virus became epidemic in human populations and antibody to this virus was found in sera of people over 70 years, the suggestion is made that the recurrence of swine virus as an epidemic agent of human influenza may be expected around 1986. Fourfold or greater increase of antibody to Swine/1930 virus was observed in about 4--5% of people infected by or immunised with H3N2 viruses. This response occurred in people who had been in touch with the epidemic influenza-A viruses Hsw1N1, H0N1, and H1N1 during the swine era of 1918 to 1956. Following immunisation with H3N2 viruses of persons showing no response to H3N2 viruses in their serum 5% did show a fourfold or greater heterotypic H.I. antibody rise to swine virus. This finding is of consequence for the diagnostic serology of influenza.

Adolescent↗

PubMed1979

Assessment of inactivated influenza-A vaccine after three outbreaks of influenza A at Christ's Hospital.

The boys of Christ's Hospital experienced outbreaks of influenza A in 1972 (A/England/42/72), in 1974 (A/Port Chalmers), and in 1976 (A/Victoria). In each outbreak, the protective effect of inactivated influenza-A vaccine was limited to those boys, not already immune, who were vaccinated for the first time with the most up-to-date strain. Revaccination with the same strain did not increase the degree of protection, and revaccination with a later strain did not afford protection against subsequent challenge. The cummulative attack-rate in the three outbreaks was similar in all groups irrespective of vaccination history. These observations suggest that annual revaccination with inactivated influenza-A vaccine confers no long-term advantage.

Adolescent↗

PubMed1976

The effect of cigarette smoking on susceptibility to epidemic influenza and on serological responses to live attenuated and killed subunit influenza vaccines.

The effects of cigarette smoking on the incidence of epidemic influenza and on the serological response to influenza vaccination with killed subunit and live attenuated vaccines have been investigated during comparative vaccine trials in Western Australia. It was found that cigarette smokers with no pre-epidemic haemagglutination-inhibiting (HI) antibody (titres of less than or equal to 12) were significantly more susceptible to epidemic influenza than non-smokers. Smokers were no more susceptible however, if they had possessed detectable pre-epidemic HI antibody. A significantly higher proportion of smokers sero-converted after receiving the live virus vaccine than their non-smoking counterparts, but this could not be correlated with pre-vaccination HI antibody titres. The longevity of the immune response to the subunit vaccine was severely depressed 50 weeks post-vaccination in smokers who had possessed little or no immunity before vaccination (titres of less than or equal to 12). This antiboyd deficit was not observed in live virus vaccines or subunit vaccinees with pre-vaccination HI antibody (titres of greater than or equal to 24). Post-vaccinal symptoms were similar regardless of vaccine group or smoking history.

Adolescent↗

PubMed1978

Lymphocyte blastogenic responses to influenza virus antigens after influenza infection and vaccination in humans.

Virus-specific in vitro cell-mediated immune responses were investigated in 20 normal volunteers who were challenged with liver influenza A/VIC/3/75 (H3N2) virus and in 13 volunteers who were vaccinated with inactivated vaccine containing A/VIC and A/NJ/8/76 (HswN1) antigens. Lymphocyte cultures were established from peripheral blood samples obtained prior to and at various times after infection or vaccination. Blastogenesis was determined by [3H]thymidine incorporation after stimulation of cultures with purified, inactivated, whole influenza viruses. Six days after infection, significantly elevated levels of blastogenesis were observed after in vitro stimulation with A viruses of hemagglutinin and neuraminidase subtypes that were the same as (H3N2) or antigenically distinct from (Heq1Neq1 or HswN1) those of the challenge virus, although maximum stimulation was noted with virus of the same hemagglutinin subtype (H3) as the challenge virus. Similar although more prolonged blastogenic responses were noted in lymphocyte cultures from vaccinees who had serum antibody rises after vaccination. The kinetics of these responses suggest that cell-mediated immunity may play a role in early events after infection and vaccination with influenza virus.

Adolescent↗

PubMed1979

Live Victoria/75-ts-1[E] influenza A virus vaccines in adult volunteers: role of hemagglutinin immunity in protection against illness and infection caused by influenza A virus.

To explore the relationship between neuraminidase immunity and the degree of attenuatíon of live influenza A virus vaccines, a comparative evaluation of three Victoria/75-ts-1[E] (Vic/75-ts-1[E]) recombinant viruses in serum hemagglutination-inhibiting-negative (titer, </=1:8) adult volunteers was performed. These three ts-1[E] viruses had a similar restriction of replication at 38 degrees C in vitro, and each possessed the two attenuating genes of the ts-1[E] donor strain (13). However, Vic/75-ts-1[E] recombinants 81 and 113 possessed both Vic/75 hemagglutinin (H3(75)) and Vic/75 neuraminidase (N2(75)), whereas Vic/75-ts-1[E] recombinant 67 had Vic/75 hemagglutinin but the N2(65) neuraminidase. Vic/75-ts-1[E] recombinant 67 was significantly more attenuated than Vic/75-ts-1[E] recombinants 81 and 113 in that fewer local and systemic signs and symptoms of illness were observed in those volunteers who received clone 67. These findings were consistent with our previous observations which suggested that the following two factors contribute to the attenuation of ts-1[E] vaccine strains in adults: (i) the attenuating effect of the two ts-1[E] genes and (ii) the neuraminidase immunity of the host. Vic/75-ts-1[E] recombinant clone 67 vaccinees developed an immunological response to the H3(75) hemagglutinin in the absence of a response to the N2(75) neuraminidase. To assess the role that anti-hemagglutinin immunity induced by an attenuated live virus vaccine plays in resistance to influenza A virus, vaccinees who received recombinant 67 were challenged with Vic/75 wild-type virus, and their responses were compared with those of Vic/75-ts-1[E] vaccinees who received recombinant 81 or 113. Each of the three groups of ts-1[E] vaccinees was significantly protected against illness induced by wild-type virus infection, although resistance was not complete. However, the clone 67 vaccinees were protected less against infection. The infection-permissive resistance induced by clone 67 resembled that previously described for inactivated neuraminidase-specific vaccines. These results suggested that a ts-1[E] recombinant that possessed the hemagglutinin of a new pandemic variant, the neuraminidase of the preceding subtype, and the two ts-1[E] ts genes would be satisfactorily attenuated for children and adults with neuraminidase immunity and could induce resistance to illness caused by the new pandemic wild-type influenza A virus.

Adolescent↗

PubMed1977

The use of transportable single-radial-diffusion immunoplates in seroepidemiological studies of influenza in the Gambia. The occurrence and persistence of antibody to influenza A/Hong Kong/68 (H3N2) virus in selected inhabitants of two rural villages.

Seroepidemiological studies of influenza in the Gambia were made using transportable single-radial-diffusion immunoplates containing A/Hong Kong/68 (H3N2) virus as antigen. The frequency and durability of antibody so detected in selected residents of two Gambian villages (Manduar and Kafuta) are described. Transportable immunoplates were found to be an effective method for the serological surveillance of influenza and to be applicable in studies in remote areas where laboratory facilities may not be available. Results indicated that infection with influenza was widespread in Manduar residents on several occasions between 1968 and 1974 and that reinfection with A/Hong Kong/68 virus or its antigenic variants occurred frequently. Serum levels of antibodies to the haemagglutinin and neuraminidase antigens of the A/Hong Kong/68 virus often persisted for only a short time (mean half-life about 28 days), particularly after first infections. Antibody persistence increased following repeated reinfection. No precise explanation can be offered at present for the relatively short persistence of antibodies in Gambians. Possible reasons include genetic and environmental factors, depressed immunological reactivity associated with concurrent infection (notably parasitic diseases), and unusually high rates of synthesis and catabolism of immunoglobulins. The value of transportable immunoplates for serological surveys and for accurate assessment of antibody persistence is discussed.

Adolescent↗

PubMed1977

Temperature-sensitive mutants of influenza A virus. XIV. Production and evaluation of influenza A/Georgia/74-ts-1[E] recombinant viruses in human adults.

The two temperature-sensitive (ts) lesions present in influenza A/Hong Kong/68-ts-1[E] (H3N2 68) virus were transferred via genetic reassortment to influenza A/Georgia/74 (H3N2 74) wild-type virus. A recombinant clone possessing both ts lesions and the shutoff temperature of 38 C of the Hong Kong/68 ts donor and the two surface antigens of the Georgia/74 wild-type virus was administered to 32 seronegative adult volunteers. Thirty-one volunteers were infected, of whom only five experienced mild afebrile upper respiratory tract illness. The wild-type recipient virus was a cloned population that induced illness in five of six infected volunteers. Therfore, the attenuation exhibited by the Georgia/74-ts-1[E] virus could reasonably be assumed to be due to the acquisition of the two ts-1[E] lesions by the Georgia/74 wild-type virus. The serum and nasal wash antibody responses of the ts-1[E] vaccinees were equivalent to those of the volunteers who received wild-type virus. The two ts lesions present in the Hong Kong/68-ts-1[E] virus have now been transferred three times to a wild-type virus bearing a new hemagglutinin, and in each instance the new ts recombination exhibited a similar, satisfactory level of attenuation and antigenicity for adults. It seems likely that the transfer of the ts-1[E] lesions to any new influenza virus will regularly result in attenuation of a recombinat virus possessing the new surface antigens.

Animals↗

PubMed1977

Reactions and serologic responses after administration of inactivated monovalent influenza A/swine virus vaccines. II. Immunization of children with influenza A/New Jersey/X-53 virus vaccines.

Reactivity and immunogenicity of two inactivated, zonally purified, ether-extracted, influenza A/New Jersey/X-53 subunit virus vaccines were studied in 103 children three to 18 years of age. Children aged nine years of younger received doses of 100 or 200 chick cell-agglutinating (CCA) units, and those older than nine years received doses of 200 or 400 CCA units. Vaccines were given intramuscularly. Two doses were given at intervals of four weeks. The vaccines were minimally pyrogenic, causing only two instances of temperatures of greater than 100.0 F. Other systemic reactions were observed infrequently. Tenderness at the site of injection occurred relatively frequently but was of no medical consequence. The geometric mean titers of homologous antibody, which ranged from 1:52 to 1:75 after administration of two doses, were statistically equivalent in all treatment groups. Titers of antibody of greater than or equal to 1:40 to the influenza A/New Jersey/8/76 virus strain were achieved by 88% of the vaccinees. We concluded that two doses of ether-extracted, subunit influenza A/New Jersey/X-53 virus vaccine were well tolerated and, when given at least four weeks apart, were serologically effective for immunization of children aged three to 18 years.

Adolescent↗

PubMed1976

Temperature-sensitive mutants of influenza A virus. XII. Safety, antigenicity, transmissibility, and efficacy of influenza A/Udorn/72-ts-1[E] recombinant viruses in human adults.

The influenza A/Hong Kong/68-ts-1[E] virus (shutoff temperature, 38 C), which possesses many characteristics desirable in a vaccine virus, was used as a donor of its two temperature-sensitive (ts) lesions to the antigenically divergent influenza A/Udorn/72 wild-type virus. Two subsets of Udorn/72-ts-1[E] recombinant viruses were evaluated in seronegative volunteers (serum titer of hemagglutination-inhibiting antibody, less than or equal 1:8). The first subset, represented by clone 13, possessed a shutoff temperature of 39 C and only one of the two ts lesions; this virus was insufficiently attenuated for use in humans. The other subset, represented by clones 16 and 24, possessed both ts lesions and a shutoff temperature of 38 C, like that of its Hong Kong/68-ts-1[E] parent. This subset, also like its ts-1[E] parent, was adequately attenuated, nontransmissible, and protective against intranasal challenge with wild-type Udorn/72 virus. The attenuation manifested by the ts mutants was not a result of their cloning in bovine kidney tissue or replication in eggs. The results suggest that the Hong Kong/68-ts-1[E] virus can be considered for use as a master strain for donation of ts lesions and thus could bring about predictable attenuation of new wild-type influenza A viruses.

Antibodies, Viral↗

PubMedDate not supplied

Neutralizing influenza antibodies, IgA and total protein in the nasopharyngeal secretions of subjects vaccinated by nasal route with the inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology.

Intranasal administration of two doses of the inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology was followed by rises in the level of neutralizing secretory influenza antibodies in 82% of the cases. The concomitant study of secretory antibody, IgA and total protein levels, as well as of the serum HAI influenza antibodies demonstrated that their evolution was parallel only in 23% of the vaccinees. The percentage of secretory antibody conversion was similar to the rate of protection conferred by the vaccine.

Administration, Intranasal↗

PubMedDate not supplied

[Experimental model of associated influenza-para-influenza infection].

An experimental model of associated influenza-parainfluenza infection has been developed. Simultaneous inoculation of mice with influenza A2/21/65 and parainfluenza type 3 or inoculation with these viruses at an interval of 24 hours was shown to produce a considerably more severe disease as manifested by the development of severe confluent pneumonias involving both lungs and death of the inoculated animals. The animals with the associated infection showed no significant difference in antibody titers or the intensity of immunity as compared with control groups (influenza or parainfluenza monoinfection). The development of the mixed infection was accompanied by the inhibition of neutrophilic and macrophage phagocytosis and inhibition of interferon production.

Animals↗

PubMed1978

T lymphocytes as an indicator in influenza vaccination, influenza and acute respiratory diseases.

Significant differences in T-lymphocyte counts in the peripheral blood of normal subject and volunteers vaccinated with live and inactivated influenza vaccines as well as patients with influenza and viral acute respiratory diseases (ARD) were demonstrated. A laboratory test using T lymphocytes was proposed for the evaluation of the safety of live influenza vaccine.

Adenoviridae Infections↗