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T R Cate

Publications and source records attributed to T R Cate.

At least 55 records · Page 3Linked to original sources
PubMed1981

Immunogenicity of influenza A/USSR (H1N1) subunit vaccine in unprimed young adults.

Purified subunit vaccines (HANAflu) containing 20 microgram hemagglutinin of influenza A/USSR/90/77 (H1N1) alone or with 1-5% whole virus were compared to commercially available vaccines for reactogenicity and immunogenicity in unprimed young adults. Reactions to all vaccines were minimal. Sera from volunteers who received two intramuscular doses of vaccine or placebo were tested by hemagglutination-inhibition and neutralization tests. HANAflu with 1 microgram (5%) whole virus added was not different in immunogenicity from commercial vaccine. Both commercial vaccine and HANAflu with 1 microgram whole virus added gave higher seroconversion rates and more neutralization titers greater than or equal to 4 log2 than HANAflu alone and HANAflu + 0.2 microgram (1%) whole virus. Thus, the HANAflu subunit vaccine alone was less immunogenic than commercial vaccine in unprimed persons. However, addition of 1 microgram (5%) whole virus, but not 0.2 microgram (1%), eliminated this difference, There may be a role for addition of small amounts of whole virus to subunit influenza vaccines to overcome lower immunogenicity in unprimed populations.

Adolescent↗
PubMed1981

Comparison of amantadine and rimantadine for prevention of type A (Russian) influenza.

The efficacies of 200 mg of daily doses of amantadine and of rimantadine for prevention of infection and illness due to influenza A/USSR/77 (H1N1) virus were compared in a double-blind, placebo-controlled study on a college campus. Frequencies of symptoms that might have been side effects of the drugs were not significantly different from those in placebo recipients. Analyses indicated that the trial was initiated late in the epidemic and that an age-related protective effect against A/USSR virus existed; seroconversion frequencies were 52/139 (37%) among 18-19-year-olds, 33/130 (25%) among 20-21-year-olds, and 5/39 (12.8%) among 22-24-year-olds. Among initially antibody-negative (less than 1 : 4 in complement fixing and neutralizing tests and less than 1 : 8 in hemagglutination inhibition tests) 18-19-year-old students, amantadine was associated with significantly fewer seroconversions (P = 0.01) and both less infection and milder illness than occurred in placebo recipients (P less than 0.05). Although rimantadine was not accompanied by reduction in frequency of seroconversions in the same age group, illness frequency and severity among seroconverters were significantly reduced when compared to placebo recipients (P less than 0.01). Amantadine and rimantadine appear suitable for use in young adults. Although other studies have suggested greater effectiveness of rimantadine than of amantadine against influenza, no evidence for this was seen in the present study which used both drugs at the same dose.

Adamantane↗
PubMed1981

A polysaccharide-protein complex from Haemophilus influenzae type b. III. Vaccine trial in human adults.

Polysaccharide-protein complex prepared from Haemophilus influenzae type b strain Eagan was evaluated for toxicity and immunogenicity in adult volunteers given intramuscular injection. Most subjects had moderate local inflammation that was maximal the day after vaccination. No lot of vaccine significantly exceeded a saline placebo in production of systemic symptoms. Neither the local nor the systemic reactions of individual subjects appeared to be related to prevaccination serum antibody titers. Serum antibody responses to the capsular polysaccharide (polyribosylribitolphosphate [PRP]) component were detected in approximately 80% of the subjects. The PRP content of the vaccine antigens varied, and the rate and extent of responses were as expected for an equivalent dose of purified PRP vaccine. Antibody responses were not enhanced by aluminum phosphate. There was no booster response to a second injection given after six months. Responses to the residual lipopolysaccharide component occurred in 80% of the subjects, primarily in the IgG class. Responses to the nonlipopolysaccharide somatic components were detected less frequently.

Adult↗
PubMed1980

Genetic approaches to attenuation of influenza A viruses for man.

The explosion of new information concerning the influenza A viral genome provides a basis for deliberate manipulation of its genes with the intent of introducing specific mutations that render influenza virus attenuated and useful for prevention of disease. Currently there is considerable effort to develop a defined set of mutant genes that confer a specific and desired level of attenuation upon any viral recombinant into which they are transferred. In this manner new antigenic variants of influenza A virus may be satisfactorily attenuated after transfer of the mutant genes. The mutant genes must be readily identifiable by simple in-vitro techniques, thus enabling the genetic basis of attenuation to be monitored directly during all phases of vaccine development, manufacture and utilization in man. We describe our experience with two sets of ts mutant genes which affect viral RNA transcription or synthesis and which effect a reproducible level of attenuation in wild-type influenza A virus.

Animals↗
PubMed1980

Bacterial adherence to pharyngeal cells during viral infection.

Adherence of bacteria to pharyngeal cells from patients with naturally acquired acute respiratory illness and from volunteers experimentally infected with influenza virus vaccine was studied. Increased adherence of Staphylococcus aureus was found in both groups. In addition, Haemophilus influenzae and Streptococcus pneumoniae type I adhered in increased numbers to cells from volunteers experimentally infected with influenza virus. Alterations in mucosal cells leading to increased bacterial adherence may play a role in the pathogenesis of suprainfection by these organisms in patients with viral respiratory diseases.

Adult↗
PubMed1980

Evaluation of influenza A/Hong Kong/123/77 (H1N1) ts-1A2 and cold-adapted recombinant viruses in seronegative adult volunteers.

Two attenuated influenza A donor viruses, the A/Udorn/72 ts-1A2 and the A/Ann Arbor/6/60 cold-adapted (ca) viruses, are being evaluated for their ability to reproducibly attenuate each new variant of influenza A virus to a specific and desired level by the transfer of one or more attenuating genes. Each of these donor viruses has been able to attenuate influenza A viruses belonging to the H3N2 subtype by the transfer of one or more attenuating genes. To determine whether these two donor viruses could attenuate a wild-type virus that belonged to a different influenza A subtype, ts-1A2 and ca recombinants of a wild-type virus representative of the A/USSR/77 (H1N1) Russian influenza strain were prepared and evaluated in adult doubly seronegative volunteers at several doses. The recombinants derived from both donor viruses were attenuated for the doubly seronegative adults. Less than 5% of infected vaccinees developed a febrile or systemic reaction, whereas five of six recipients of wild-type virus developed such a response. The 50% human infectious dose (HID(50)) for each recombinant was approximately 10(5.0) 50% tissue culture infective doses. The virus shed by the ts-1A2 and ca vaccinees retained the ts or ca phenotype, or both. This occurred despite replication of the recombinant viruses for up to 9 days. No evidence for transmission of the ca or ts-1A2 recombinant virus to controls was observed. A serum hemagglutination inhibition response was detected in less than 50% of the infected vaccinees. However, with the more sensitive enzyme-linked immunosorbent assay, a serological response was detected in 100% of the ca vaccinees given 300 HID(50) and approximately 70% of ca or ts vaccinees who received 10 to 32 HID(50) of virus. These results indicate that the recombinants derived from both donor viruses were satisfactorily attenuated and were stable genetically after replication in doubly seronegative adults although they induced a lower serum hemagglutination inhibition response than that found previously for H3N2 ts and ca recombinants.

Adult↗
PubMed1980

Microneutralization test for influenza A and B and parainfluenza 1 and 2 viruses that uses continuous cell lines and fresh serum enhancement.

A modified microneutralization test for influenza A and B and parainfluenza 1 and 2 viruses was developed. Use of continuous cell lines (Madin-Darby canine kidney and LLC-MK2), hemagglutination for virus detection, and transfer plates and other microtiter equipment resulted in a highly mechanized technique suitable for titrating large numbers of sera easily and relatively inexpensively. Titers of heat-inactivated human sera were enhanced 0.5 to 3.5 log2 by addition of fresh hamster or human serum to the test. Seroconversion rates and identification of seronegative persons were not changed by fresh serum enhancement, but the magnitude of seroconversion was often increased and the distribution of positive titers was broadened. For influenza A and B, seroconversion rates in the microneutralization test were equivalent to those obtained in rhesus monkey kidney tube neutralization tests. For influenza B, seroconversion rates by micro-neutralization were almost double those obtained with the hemagglutination inhibition test, but the rates were similar for influenza A/USSR (H1N1). Preexisting microneutralization titers correlated well with resistance of infection with influenza B. Limited experience with parainfluenza 1 and 2 was similar to previously reported findings with the tube neutralization test.

Adult↗
PubMed1979

A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis.

We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.

Adolescent↗
PubMed1979

Efficacy of purified influenza subunit vaccines and relation to the major antigenic determinants on the hemagglutinin molecule.

Inactivated whole-virus vaccine of influenza A/Scotland/74 (H3N2) virus containing 700 or 1,400 chick cell-agglutinating (CCA) units, a purified subunit vaccine of equivalent dosage, or placebo were studied in 186 adult volunteers. Placebo was least reactogenic, 1,400-CCA unit whole-virus vaccine was most reactogenic, and others were intermediate. Vaccines were equally antigenic, and delineation of antibody specificities revealed antibody cross-reacting with A/Hong Kong/68 (H3N2) virus in all sera. Antibody specific for A/Hong Kong/68 virus was found in 82% of sera and for A/Scotland/74 virus in 46%. When compared with volunteers given placebo, volunteers given 700 CCA units of subunit or whole-virus vaccine exhibited significant protection against infection with live A/Scotland/74 virus. Infections in vaccinees occurred only in those with low titers of antibody to A/Scotland/74 virus, and this antibody was of the cross-reacting type. Persons with moderate and high levels of antibody resisted infection regardless of the absence or presence of antibody specific for A/Scotland/74 virus. Purified subunit vaccines provide an alternative to whole-virus preparations in primed individuals. Efficacy of vaccines may be dependent on the nature of the antibody response.

Adolescent↗
PubMed1979

Temperature-sensitive mutants of influenza A virus: evaluation of the A/Victoria/75-ts-1A2 temperature-sensitive recombinant virus in seronegative adult volunteers.

An influenza A virus recombinant bearing the surface antigens of the A/Victoria/3/75 (H3N2) strain and the two ts genes of the A/Udorn/72-ts-1A2 virus was evaluated for attenuation, antigenicity, and protective effect in 42 doubly seronegative adult volunteers (i.e., individuals who lacked detectable serum antibodies for the hemagglutinin and neuraminidase antigens). This recombinant, which had a 37 degrees C shutoff temperature for plaque formation and ts mutations on the genes thought to code for the P1 and P3 polymerase proteins, infected 90% of the volunteers. Of the volunteers, 5% developed mild coryza or rhinitis but other signs or symptoms were not observed, indicating that the A/Victoria/75-ts-1A2 recombinant was more attenuated than the A/Victoria/75-ts-1[E] recombinant. Vaccinees shed virus for a shorter interval and at a lower titer than did the A/Victoria/75-ts-1[E] vaccinees. Each ts-1A2 isolate retained the ts phenotype indicating that the recombinant was stable genetically in doubly seronegative adults. Finally, the ts-1A2 recombinant induced significant resistance to subsequent challenge with A/Victoria/75 wild-type virus.

Adult↗
PubMed1979

Appearance of rosette-forming macrophages in the lungs of influenza virus-infected mice.

Approximately one fifth of the macrophages obtained from the lungs of mice infected 2 to 5 days with influenza A/HK virus were found to rosette well with either unmodified human, chicken, or guinea pig erythrocytes, but not with erythrocytes from hamsters, sheep, or mice. Rosette-forming macrophages were seldom seen in suspensions from uninfected mice (3+/-3%) or mice infected 24 h previously (3+/-3%). Rosette formation was not due to virus hemadsorption, as indicated by the failure of specific antiserum to influenza virus to block rosette formation; by the induction of comparable levels of rosette-forming macrophages in the lungs of mice infected with herpes simplex virus type 2, a nonhemadsorbing virus; and by the inhibition of rosette formation at 4 degrees C. Instead, rosette formation appeared to be directly related to macrophage elicitation or activation since nonstimulated macrophage populations such as peripheral blood monocytes, macrophages from uninfected lungs, or noninduced peritoneal macrophages were not observed to rosette to any significant extent. Furthermore, peritoneal macrophages induced with filter-sterilized normal horse serum rosetted at levels comparable to that observed with cells from infected lungs. These results indicate that hemadsorption alone can not be used as a criterion of virus infection of macrophages. However, rosette formation may serve to identify macrophage subpopulations which are active in host defense against viral infections.

Animals↗
PubMed1978

Temperature-sensitive mutants of influenza A virus: evaluation of A/Victoria/3/75-ts-1[E] recombinant viruses in volunteers.

The Hong Kong/68-ts-1[E] virus and its Udorn/72 and Georgia/74 recombinants, which have a 38 degrees C shutoff temperature and a ts lesion(s) on the genes coding for the P3 and NP proteins, were adequately attenuated and immunogenic in adult volunteers who lacked serum hemagglutination-inhibiting antibody (titer, </=1:8), but who possessed serum neuraminidase-inhibiting antibody. Two Victoria/75-ts-1[E] clones that also had a 38 degrees C shutoff temperature and a ts lesion(s) on the same two genes were administered to adult volunteers who lacked both serum hemagglutination-inhibiting antibody (titer, </=1:8) and neuraminidase-inhibiting antibody (titer, </=1:4). In contrast to the behavior of the earlier ts-1[E] recombinants, the Vic/75-ts-1[E] recombinants retained the capacity to cause febrile, systemic illness. However, the recombinants were attenuated compared with wild-type virus. The Vic/75-ts-1[E] virus vaccinees shed a larger amount of virus for a longer time than the previous ts-1[E] vaccinees, but they shed less virus than volunteers infected with wild-type virus. The ts-1[E] virus shed retained its ts phenotype in most instances and failed to spread to susceptible contacts. Vaccinees were partially protected against homologous wild-type virus challenge. The failure of HK/68, Udorn/72, and Georgia/74 ts-1[E] vaccinees to develop systemic reactions may reflect the presence of neuraminidase immunity before infection. In this situation, attenuation probably resulted from the degree of defectiveness of the ts-1[E] recombinant virus and the existence of neuraminidase immunity in the recipients. The 50% human infectious dose of the Vic/75 ts-1[E] virus was less than 10(5.2) 50% tissue culture infective doses. This suggests that at the time of a pandemic shift involving both the hemagglutinin and neuraminidase glycoproteins, a small amount of live virus vaccine might be effective in initiating infection.

Antibodies, Viral↗
PubMed1978

Morphological and cytochemical characterization of cells infiltrating mouse lungs after influenza infection.

To initiate evaluation of the cell-mediated immunological response to influenza virus in a major site of disease, lung cells were obtained by transpleural lavage from lungs of uninfected mice and from those infected 3 or 6 days previously with 5 50% mouse infectious doses (MID(50)) of avirulent (P3) or virulent (P9) influenza A Hong Kong (H3N2) virus. The number of cells recovered by lavage was dependent on the dose, time after inoculation, and the type of virus used for inoculation. Although lavage pools were shown to contain peripheral blood leukocytes, this contamination was shown to be consistently less than 5% of the total leukocytes harvested. Among the ca. 0.75 x 10(6) lavage cells obtained from each uninfected mouse, about 90% were macrophages or lymphocytes in approximately equal proportion. T, B, and null (lyphocytes lacking theta or surface immunoglobulin markers) lymphocytes averaged 23, 9, and 7% of cells in these suspensions, respectively. After infection with either P3 or P9 virus, increased numbers of activated macrophages and lymphoblasts were observed. The major change during P3 infection was an increase in absolute numbers of null lymphocytes. In contrast, during P9 infection, T and B lymphocytes and macrophages progressively increased in absolute numbers while null cells decreased. These data suggest that cell-mediated immunological responses to influenza virus occur in the lung during infection, but that the responses to virulent and avirulent variants may differ both qualitatively and quantitatively.

Animals↗
PubMed1978

Cellular changes in lungs of mice infected with influenza virus: characterization of the cytotoxic responses.

Transpleural lavage of lungs from uninfected C3H mice yielded an average of 300,000 leukocytes per mouse. This number increased eightfold within 6 days after intranasal inoculation with virulent influenza A/Hong Kong/68 (H3N2) virus. Macrophages and lymphocytes in approximately equal numbers comprised 90% or more of the leukocytes both before and during infection. B, T, and null lymphocytes comprised, respectively, 9, 21, and 18% of the leukocytes before infection and 7, 26, and 5% by day 6. In absolute numbers, macrophages and T lymphocytes provided the major increments during infection. Cytotoxic activity of mononuclear cells from lung lavages was compared in a chromium release assay using syngeneic L929 target cells with the activity of mediastinal lymph nodes, spleens, and peripheral blood of uninfected and infected C3H mice. Nonspecific cytotoxicity for target cells infected with H3hkNeq1 or B/Lee influenza virus was found with mononuclear cells from uninfected mice. This activity tended to be highest with lavage leukocytes and was associated with adherent cells, presumably macrophages. Increased virus-specific cytotoxicity was detected with lavage cells by day 6 and persisted through day 9, the period of maximal pneumonia. Similar cytotoxic activity also appeared in cells from the nodes and spleen at this same time but was not detected in peripheral blood cells. The virus-specific cytotoxicity of lavage cells was due largely to a nonadherent cell possessing Fc receptors and theta antigen but lacking C3 receptors; these properties are compatible with actively cytotoxic T lymphocytes. The cytological characteristics of the infiltrating leukocytes and the cytotoxicity data suggest that the local T cell response to influenza virus infection in the lung is a major contributor to the pneumonia observed in this mouse model.

Animals↗