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Biomedical subjects

R Pyhälä

Publications and source records attributed to R Pyhälä.

At least 37 records · Page 2Linked to original sources

Early kinetics of antibody response to inactivated influenza vaccine.

The aim was to examine the rapidity of haemagglutination inhibiting (HI) antibody response induced by immunization with a current inactivated trivalent influenza vaccine. Five to six sequential serum samples collected in autumn 1992 from each of 68 vaccinees in three age groups were studied for HI antibodies to ten influenza virus strains representing vaccine and epidemic viruses. Geometric mean titres, response rates and protection rates are presented. Response rates of > 70% were overall, but not until two weeks after the vaccination. Significant two- and four-day post-vaccination antibody responses were detected only occasionally. In previously vaccinated persons, average antibody titres to some of the viruses decreased during the first days after the vaccination. In the subsequent samples, the titres remained lower than in persons who were not vaccinated against influenza in preceding years. Protection against influenza infection may be frequently developed not until two weeks after vaccination. This has relevance to prophylactic administration of amantadine and rimantadine when an influenza A outbreak is imminent and the vaccination is late.

Journal Article↗

Vaccination-induced HI antibody to influenza A(H1N1) viruses in poorly primed adults under circumstances of low antigenic drift.

In Autumn 1990, trivalent split influenza virus vaccine containing A/Taiwan/1/86(H1N1) was used to immunize healthy female employees (n = 104). The 11-12 amino acid differences in the HA1 domain of virus haemagglutinin between A/Taiwan/1/86 and representative epidemic H1N1 strains in Finland in 1991 did not result in lowered haemagglutination-inhibiting (HI) antibody responses to the latter viruses. In fact, higher prevaccination, postvaccination and postepidemic antibody titres were recorded against the new field strains than against the vaccine virus; the highest being against field strains grown exclusively in MDCK cell cultures. This pattern is primarily explained by differences in the sensitivity of the viruses for detecting HI antibodies. Postvaccination protection rates of 98-100% for the MDCK-grown avid viruses were noted in subjects who exhibited prevaccination antibody. Lower protection rates were recorded in initially seronegative subjects, the lowest (54-57%) being among older people, i.e. among vaccines born in 1930-1955 (p < 0.001). Moreover, conspicuous decreases in protection rates were detected during the following epidemic season in the initially seronegative subjects. Diagnostic findings during outbreaks due to H1N1 subtype viruses also support the impression that many middle-aged people are poorly primed. Thus, vaccination with two doses may be worth considering when such people join the high-risk group and receive influenza vaccine for the first time.

Adult↗

Immune response to inactivated influenza virus vaccine: antibody reactivity with epidemic influenza B viruses of two highly distinct evolutionary lineages.

Vaccination of adults (healthy female employees potentially capable of transmitting influenza to high-risk persons; n = 104) in autumn 1990 with a trivalent influenza virus vaccine containing B/Yamagata/16/88 induced a low antibody response to B/Finland/150/90, a recent variant of B/Victoria/2/87-like viruses, as compared with the antibody response to B/Finland/172/91, a current variant in the lineage of B/Yamagata/16/88-like viruses. Up to the end of the epidemic season, the antibody status declined but was still significantly better than before the vaccination. The results suggest that the vaccine strain was appropriate for the outbreak of 1990 to 1991 in Finland, but may provide unsatisfactory protection against B/Victoria/2/87-like viruses. Evidence is given that use of Madin-Darby canine kidney (MDCK)-grown virus as an antigen in the haemagglutination inhibition test (HI) may provide more reliable information about the protective antibodies than use of untreated or ether-treated egg-grown viruses. Significantly higher postvaccination and postepidemic antibody titres were recorded among subjects who exhibited the antibody before vaccination than among seronegative subjects. A significantly higher response rate among initially seronegative people than among seropositive people was recorded for antibody to B/Finland/150/90, but no clear evidence was obtained that the pre-existing antibody could have had a negative effect on the antibody production.

Adult↗

Evolution of influenza B/Victoria/2/87-like viruses: occurrence of a genetically conserved virus under conditions of low epidemic activity.

Nucleotide sequence analysis of the gene region coding for the HA1 domain of the influenza B virus haemagglutinin was performed on seven field strains isolated during the 1989 to 1990 season and two field strains isolated in 1985 and 1988 in Finland. All isolates were antigenically and genetically related to B/Victoria/2/87 virus and distinct from B/Yamagata/16/88 virus. The three strains isolated at the beginning of the 1989 1990 season in Turku were almost identical to an American variant (B/Texas/37/88-B/Ohio/10/88) of the previous season, whereas the four strains isolated later in the 1989 to 1990 season in Helsinki formed a new group of heterogeneous viruses. The phylogenetic tree compiled suggests that the two branches had evolved from a common origin, probably in 1987.

Amino Acid Sequence↗

Gm allotypes influence the production of IgG3 but the effect is age-dependent.

Serum concentrations of IgG3 were found to be higher in Gm-f-positive (= b-positive) than in f-negative individuals except in young children. Young children aged 3-4 months had a mean concentration of 0.24 g/l of IgG3 regardless of allotype. The concentration gradually rose with age in f-positive individuals to a geometric mean of 0.56 g/l in adults but it remained essentially unchanged in f-negative people. A corresponding allotype effect was seen in influenza-specific antibody responses. While the total IgG response (mainly IgG1) was equally strong in f-positive and in f-negative patients, f-positive (= b-positive) patients produced more IgG3 antibodies than f-negative patients. The difference between geometric mean values of opposite homozygotes (f/f versus f-negative) was 2.3-fold (p = 0.0113). This finding indicates that the b-positive gamma-3 allele is more productive than the g-positive allele.

Adult↗

Influenza epidemics and anencephaly.

To explore the postulated association between maternal influenza and congenital defects of the central nervous system, 14 virologically verified epidemics in Finland, 1969-82, were studied. Mothers of 248 anencephalic children were grouped into those whose first trimester had occurred during an epidemic period and those whose pregnancy had commenced during a non-epidemic period. No significant differences in prevalence of anencephaly were noted in these groups.

Adult↗

Use of vaccines for respiratory infections. Strategies for influenza and pneumococcal vaccines.

Indications for use of influenza and pneumococcal vaccines are reviewed in view of current knowledge of the incidence, risk factors and etiology of pneumonia in adults. It appears that both vaccines contribute equally in an almost additive fashion to predicted benefits of vaccination; therefore, both should be used for maximum benefit. Target groups for vaccination include both elderly persons (e.g. 65 years and older) and younger ones who have medical risk factors that increase the likelihood or severity of pneumonia.

Bacterial Vaccines↗

Host cell-mediated selection of influenza A (H3N2) virus variant subpopulations: lack of association between antigenic and receptor-binding properties.

During the outbreak of influenza due to A (H3N3) viruses in Finland in 1985/6 virus pairs were isolated from the same clinical specimens in embryonated hens' eggs (CE) and in canine kidney cell cultures (MDCK). Some of these isolates, the E and M pairs, were distinguished by their reactions in haemagglutination inhibition (HI) tests carried out using polyclonal antisera, and by receptor-binding properties, as evidenced by differences in their elution activity from erythrocytes. Passage of the E- and M-virus isolates in the foreign host affected their serological characteristics, but the E virus did not convert to an M-like virus and the M virus did not convert to an E-like virus. Returning the viruses to grow in the host used for their isolation changed the serological reactions so that they were once more close to the reactions of the original isolates. This contrasts with the changes in receptor-binding properties. Rapid elution from hen erythrocytes, which has been described as a property of viruses binding to the SA alpha 2,3Gal sequence in preference to SA alpha 2,6Gal, characterized the virus passages grown solely in MDCK cell cultures. Cultivation of the M virus in CE, at any stage of its passage history, made the virus irreversibly incapable of elution. The M virus was more sensitive than the E virus to HI antibodies against heterologous viruses of the H3N2 subtype, and, when used as an antigen in HI serology, it more frequently (90% vs. 69%; P less than 0.01) detected diagnostic antibody responses in patients infected with viruses of this subtype in 1985/6. Use of antigens with a different passage history in HI serology provided evidence that this superiority, which may be due to the ability of the virus to pick out anamnestic antibody responses, is unrelated to the receptor-binding peculiarity of the M virus under consideration. The results support the concept that the host cell can select a diversity of virus variant subpopulations from a single clinical specimen during isolation and subsequent cultivation procedures. Moreover, the MDCK-grown influenza viruses may correspond better than the egg-grown isolates to the natural epidemic viruses.

Animals↗

Antigenic analysis of intraepidemic variants of influenza A (H3N2) viruses by hyperimmune rat antisera.

Hyperimmune rat antisera prepared against 5 recent antigenic variants of influenza A (H3N2) viruses were studied for haemagglutination inhibiting (HI) antibodies to the homologous and the heterologous viruses. The ratios of homologous to heterologous reactions varied from one animal to another in immunizations with each of the immunogens. Some antisera exhibited a ratio high enough to allow differentiation of the epidemic variants and demonstration of an intraepidemic heterogeneity of field strains isolated during the outbreak of 1985/86. The variation of cross-reactions of polyclonal antisera may reflect differences in the range of specificities of anti-haemagglutinin antibodies produced by individual animals. The significance of this finding in the classification of influenza A (H3N2) viruses is discussed. Lack of nonspecific inhibitors interfering with the HI test is an additional advantage of hyperimmune rat antisera in typing influenza A and B virus isolates.

Animals↗

Egg-grown and tissue-culture-grown variants of influenza A (H3N2) virus with special attention to their use as antigens in seroepidemiology.

A field strain of influenza A (H3N2) virus isolated in embryonated eggs during the 1984-5 influenza outbreak (A/Finland/13/85E) was compared in an antigenic analysis with virus from the same clinical specimen isolated in MDCK cell cultures (A/Finland/13/85M). The M-virus appeared to be more sensitive to haemagglutination-inhibiting antibodies against heterologous viruses than did the E-virus. The results of propagation and plaque purification experiments support the hypothesis that a single clinical specimen may consist of distinct antigenic variant subpopulations promoted selectively by the host during isolation procedures. Receptor-binding properties are discussed as a possible explanation for this selectivity. A set of 471 paired sera consisting of pre-epidemic and post-epidemic specimens taken from the same subjects in 1984-5 was studied for haemagglutination-inhibiting antibodies to six influenza A (H3N2) virus strains, including the E-virus and the M-virus from A/Finland/13/85. Of the antigens used, the M-virus detected significant antibody increases more frequently than did the E-virus (10.0 v. 5.9%). The superiority of the M-virus may rest primarily in its ability to pick out anamnestic antibody responses. Irrespective of this cross-reactivity, pre-epidemic antibody to the M-virus was fairly well associated with protection. In the set of sera (230 specimens) collected in summer 1985 to represent different age groups, the antibody status against the M-virus was significantly better than the status against the E-virus. The results suggest that, at least in some instances, antibody to MDCK-grown virus is a more accurate indicator of the immune status of a community than antibodies to egg-grown virus variants.

Adolescent↗

Lack of clinical exacerbations in adults with chronic asthma after immunization with killed influenza virus.

The effects of immunization with killed influenza virus vaccine were assessed by comparison with placebo in a double-blind study of 318 adult patients with chronic asthma. The patients were randomly allocated to active vaccine and placebo. No difference was observed in peak expiratory flow rate or in clinical symptoms of bronchial obstruction between the groups receiving active vaccine and placebo during the first week after immunization. The data were analyzed separately for age, sex, duration of the disease, hypersensitivity to aspirin (acetylsalicylic acid), atopic status, patients with a history of attacks of asthma induced by viral infections, patients with a diurnal variation of baseline peak expiratory flow of 20 percent or more, and patients receiving continuous oral steroid medication, but none of these factors seemed to predict any short-term adverse effects of vaccination. Follow-up for eight months after the vaccination revealed no differences in asthmatic symptoms between the patients treated with active vaccine and those receiving placebo. The antiviral antibody response to vaccination was normal. The possible protection provided by the vaccination against exacerbation of asthma induced by influenza could not be evaluated, since the influenza epidemic expected during the season failed to occur in Finland. It is concluded that immunization with killed influenza vaccine is safe and is not associated with any significant side effects in adult patients with chronic asthma.

Adult↗

Intraepidemic heterogeneity of influenza A (H3N2) viruses in 1985: antigenic analysis and sensitivity to non-specific inhibitors.

During the influenza outbreak of 1984-85 22 strains of H3N2 viruses were isolated in Finland. An intra-epidemic heterogeneity was demonstrated in an antigenic analysis by haemagglutination inhibition test with antisera produced in rats. The strains could be classified into three groups which corresponded to the following reference strains: group I: A/Hong Kong/1/84, A/Hong Kong/3/84; group II: A/Philippines/2/82; group III: A/Caen/1/84. Seven of the isolates were entirely insensitive to gamma-inhibitors of guinea-pig sera, which is in contrast to the small number of these viruses found among H3N2 strains isolated in the 1970s. The insensitive strains could not be isolated until the second or third passage through the eggs, whereas about half of the sensitive and intermediate strains were already isolated during the first passage. Conversions in reactivity with gamma-inhibitors could be detected only from an intermediate or an insensitive virus to a sensitive virus when several strains were passed serially in ovo and in MDCK cultures. The findings suggest that the gamma-inhibitor-insensitive strains corresponded well to the viruses of the human host or arose from dimorphic virus populations under an arbitrary selection of terminal dilution conditions prevailing during isolation in eggs. The insensitive strains did not differ substantially from the sensitive viruses in their ability to agglutinate erythrocytes of different laboratory animals or in their disagglutination patterns. On the other hand, propagation of viruses in MDCK cultures had an effect on these properties. The results are discussed with respect to Q phase variants and receptor binding properties.

Antigens, Viral↗

Enzyme immunoassay, complement fixation and hemagglutination inhibition tests in the diagnosis of influenza A and B virus infections. Purified hemagglutinin in subtype-specific diagnosis.

The efficacy of enzyme immunoassay (EIA) in detecting diagnostic antibody rises to influenza A and B viruses was compared with complement fixation (CF) and hemagglutination inhibition (HI) tests in 455 patients with an acute respiratory infection. EIA and HI detected significantly more diagnostic antibody rises against influenza A than the CF method (96 and 87 vs. 47, respectively). In the case of influenza B significantly more diagnostic influenza B antibody rises were observed by EIA than by CF or HI (59 vs. 37 and 40, respectively). In most of the cases antibody rises in EIA were found in both IgG and IgA isotypes whereas increases in IgM antibodies were seen less frequently. Purified hemagglutinins (HA) were prepared from influenza A HI- and H3-subtypes and from influenza B viruses and used as antigens in EIA and the results were compared with those of HI. Infections caused by influenza A HI-subtype showed good homologous antibody responses in EIA but heterologous antibody responses to H3-subtype and influenza B HAs were frequently observed. Heterologous responses were clearly less frequent in patients with infections caused by the H3-subtype. Influenza B infections occasionally raised HA antibodies against influenza A H1-subtype but not to the H3-subtype. Interestingly, HI detected these heterologous responses at least as frequently as EIA. When whole viruses were used as antigens in EIA, subtype specificity was not observed and cross-reactions between influenza A and B virus antibodies were found. These observations suggest that, although EIA can show greater diagnostic efficacy over HI and CF methods, HI is still the serological method of choice in determining the causative subtype of influenza A virus infection.

Adolescent↗

The HI test modified by ether treatment in the sero-epidemiological surveillance of influenza B.

Ether-treated influenza B haemagglutination inhibition (HI) antigen was used in a study of serum collections from three different epidemic seasons. For diagnostic purposes, ether treatment increased the efficacy of the HI test by about 50% over the conventional HI technique, raising it to the same level of sensitivity as the complement fixation (CF) test. The treatment reduced the specificity of the HI test, but its reliability in the diagnosis of influenza B infections was only slightly diminished. With regard to evaluation of the immune status of a given population, an HI test using ether-treated antigen from the epidemic influenza B strain seems to give more relevant information about the antibody level associated with protection than a conventional HI test using untreated virus antigen.

Antibodies, Viral↗

Antibody status to influenza A/Singapore/1/57(H2N2) in Finland during a period of outbreaks caused by H3N2 and H1N1 subtype viruses.

The incidence of haemagglutination inhibition (HI) antibody (titre greater than or equal to 12) to influenza A/Singapore/1/57(H2N2) in sera collected from a Finnish population in the summer of 1981 was 58%. Subjects born after 1968 were essentially seronegative, and a comparable low HI antibody status was also recorded among the elderly, the lowest being in people born during the period 1901-10. A small increase in antibody titre to the H2N2 virus was observed in the different age groups after infections with the H3N2, but not the H1N1, subtype influenza A viruses. The heterotypic response, which could be due to HI or NA antibodies, was restricted almost exclusively to subjects already exhibiting this antibody in acute phase sera. Moreover, the anamnestic boosting was not as strong as that described in earlier studies from samples collected at the beginning of the present era of H3N2 viruses. At population level, the HI antibody status to H2N2 was about the same at the beginning and end of the follow-up period which covered eight epidemic seasons. The results are discussed with respect to the doctrine of 'original antigenic sin' and to the threat of re-emergence of the H2N2 viruses.

Antibodies, Viral↗

Serum acute-phase glycoproteins and immune complexes in relation to smoking and respiratory symptoms: an epidemiological study.

A nephelometric assay of concanavalin A binding was used to measure serum acute-phase glycoproteins in young conscripts, in middle-aged males, and in adults with persistent respiratory symptoms. The findings in conscripts, irrespective of the smoking status, did not differ from those in blood donors, whereas, a strikingly higher portion (38%) of the middle-aged heavy smokers exhibited elevated values. In subjects with persistent respiratory symptoms the corresponding figure was even higher (52%), but no difference was recorded between smokers and non-smokers. Elevated amounts of circulating immune complexes, as measured by conglutinin-binding assay, were detected in 6% of the middle-aged males and in 20% of the subjects with persistent respiratory symptoms.

Acute-Phase Proteins↗