Changes in the antibody status of a population following epidemic infection by influenza virus A2/Hong Kong/1/68

The haemagglutinin of influenza virus A2/Hong Kong/1/68 was shown to be markedly different from that of previously isolated A2 virus strains. No haemagglutination-inhibiting (HI) antibody to A2/Hong Kong/1/68 virus was detected in serum specimens collected in 1966 from persons aged 60 years or less. In contrast, HI antibody tests with 270 sera collected in 1968 indicated that 9·6% had demonstrable HI antibody at low titres, and 35·2% of 454 postepidemic (1969) sera had demonstrable HI antibody at relatively high titres. Most sera from persons aged 80 years and more collected in 1968 and 1969 had demonstrable HI antibody to influenza virus A2/Hong Kong/1/68. No HI antibody to the Hong Kong virus was detected in pre-epidemic sera from children aged 6 months to 3 years, whereas 32% of postepidemic sera had HI antibody. The acquisition of HI antibody to A2/Hong Kong/1/68 was not accompanied by an increase in the incidence or titres of HI antibody to heterotypic A2 influenza viruses. For sera from children aged 4-11 years, an increase of HI titre to heterotypic A2 influenza was found.     

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.     

Frequency of naturally occurring antibody to influenza virus antigenic variants selected in vitro with monoclonal antibody.

Antigenic variants of A/Texas/77 (H3N2) virus were selected in vitro using monoclonal antibody to virus haemagglutinin (HA). The antigenic variants and parental A/Texas/77 viruses were used to to evaluate the frequency of anti-HA antibodies in the sera of children and adults using single-radial-haemolysis (SRH) tests. Twenty to 41% of selected sera from adults, which contained antibody to the parental A/Texas/77 virus, failed to react with the different antigenic mutant viruses. A higher proportion of sera from children (37-58%) failed to react with the antigenic variants. Certain human sera and particularly those of children would appear to possess a more limited antibody repertoire to influenza HA, potentially allowing new antigenic variants to escape neutralization and spread in the community.     

Studies in swine of Asian influenza virus

This article reports on experiments with 6- to 8-week-old pigs infected with a human isolate of Asian strain influenza virus and on the successful passage of this virus into a second group of pigs. These findings are discussed in relationship to negative results obtained by others when swine sera, collected from apparently healthy animals before and after the recent Asian influenza epidemic, were tested for the presence of complement-fixing and haemagglutination-inhibiting antibodies.Six "normal" pigs were inoculated intranasally with 1.0 ml of fluid containing approximately 3 200 000 EID(50) of Asian influenza virus. Clinical evidence of disease was not apparent, but Asian strain virus was isolated from four of the pigs and the development of haemagglutination-inhibiting antibody to A/Asia/Japan/305/57 antigen was detected in all of them. Virus isolated from the first group was inoculated intranasally into another group of six "normal" pigs. Clinical evidence of illness was also absent in this group, but Asian strain virus was isolated from five pigs. Haemagglutination-inhibiting antibody developed in all six pigs but complement-fixing antibody in none.The authors conclude that the available evidence indicates that swine did not play a significant role in the epidemiology of the Asian influenza epidemic in the USA, and that the Asian strain appears not to have established itself in swine.     

Prevalence of human (H1N1) influenza virus-antibody in Japanese swine

A total of 571 swine sera collected at an abattoir in the city of Obihiro, Hokkaido during the period February-November 1984 were tested for antibody against human (H1N1) influenza virus strains. A high prevalence of antibody was observed for only 3 months from April to June in that year, in 81/180 sera (45.0%) to A/USSR/92/77 strain and in 50/180 sera (27.8%) to a current epidemic strain (A/Hokkaido/1/84). Some cross-reactions were observed between the A/USSR/92/77 and A/Hokkaido/1/84 antibodies (r = 0.75). Only minor relationships were noted between the A/New Jersey/8/76 (swine type H1N1) and A/USSR/92/77 (r = 0.35) or A/Hokkaido/1/84 (r = 0.51) antibodies. Absorption of sera positive for antibody to the A/Hokkaido/1/84 strain with the homologous virus strain removed all detectable antibodies, while the absorption of the sera with the A/New Jersey/8/76 strain produced incomplete absorption in one half of the sera tested. These results strongly suggest that the swine became infected with a human H1N1 virus as piglets during an epidemic of influenza which occurred in the human population during January and February 1984.     

Prevalence of human (H1N1) influenza virus-antibody in Japanese swine.

A total of 571 swine sera collected at an abattoir in the city of Obihiro, Hokkaido during the period February-November 1984 were tested for antibody against human (H1N1) influenza virus strains. A high prevalence of antibody was observed for only 3 months from April to June in that year, in 81/180 sera (45.0%) to A/USSR/92/77 strain and in 50/180 sera (27.8%) to a current epidemic strain (A/Hokkaido/1/84). Some cross-reactions were observed between the A/USSR/92/77 and A/Hokkaido/1/84 antibodies (r = 0.75). Only minor relationships were noted between the A/New Jersey/8/76 (swine type H1N1) and A/USSR/92/77 (r = 0.35) or A/Hokkaido/1/84 (r = 0.51) antibodies. Absorption of sera positive for antibody to the A/Hokkaido/1/84 strain with the homologous virus strain removed all detectable antibodies, while the absorption of the sera with the A/New Jersey/8/76 strain produced incomplete absorption in one half of the sera tested. These results strongly suggest that the swine became infected with a human H1N1 virus as piglets during an epidemic of influenza which occurred in the human population during January and February 1984.     

Use of monoclonal anti-haemagglutinin antibodies for the “In vitro” selection of a sequential influenza virus antigenic variant

A sequential antigenic variant of the A/Texas/77 (H3N2) influenza virus was obtained in vitro using a monoclonal antibody against the haemagglutinin (HA) of the antigenic variant V18 previously selected in vitro from the parental Texas virus. The sequential antigenic variant, designated DV1, the V18 antigenic variant and the parental A/Texas/77 viruses were used to evaluate the frequency of anti-haemagglutinin antibodies in human sera in single radial haemolysis assays. Twenty six of 100 children's sera, which contained antibodies to the parental A/Texas/77 virus, failed to react with the V18 antigenic variant. A higher proportion of sera (42%) failed to react with the DV1 antigenic variant with alterations in two different antigenic determinants with respect to the parental virus. The results are discussed in relation to the mechanism of antigenic drift and to the in vivo reaction of antigenic variants selected in vitro.Corresponding author.     

Influenza A neuraminidase antibodies in children and young adults studied by serum absorption.

A study is described of influenza A anti-neuraminidase antibodies in the sera of young people of three different groups. Each serum was individually absorbed with viruses containing the N2 neuraminidases of 1957, 1968 and 1972. Rabbit antisera prepared against the viruses were similarly absorbed. Results obtained with the animal sera suggested that these neuraminidases were antigenically distinct, but the human sera had a broader range of anti-neuraminidase activity and gave indication of asymmetric antigenic relationships. Earlier workers who surveyed anti-haemagglutinin antibodies reported that the virus of primary infection absorbed all antibodies, and the virus of secondary infection only those directed against itself. We too found that the virus of secondary infection absorbed only homologous anti-neuraminidase antibody. However, although the primary infecting virus did absorb some secondary antibody, this absorption was incomplete and it lessened with the lengthening of the time interval between the primary and secondary infecting viruses. A similar pattern was seen with anti-haemagglutinin antibodies. Absorption of anti-neuraminidase antibodies from human sera proved much more difficult than absorption of anti-haemagglutinin antibodies particularly after repeated influenza virus infections. The relative rarity of antigenic shift in the neuraminidase subunit also creates problems in the interpretation of results of serum neuraminidase antibody surveys.     

Cross-reactivity of influenza A (H3N2) hemagglutination-inhibition antibodies induced by an inactivated influenza vaccine

The antigenic drift of influenza A (H3N2) virus in 2003-2004 necessitated a change in the vaccine from the A/Panama to the A/Wyoming strain for the 2004-2005 season. Using hemagglutination inhibition, we therefore tested antibodies in sera of 39 individuals (mean age 64.6 years) at the end of the 2003-2004 season for cross-reactivity to vaccine strains and H3N2 antigens subject to antigenic drift. Antibodies against both A (H3N2) Panama and Wyoming developed in 5/13 (38.5%) unvaccinated individuals, whereas, 22/26 (84.6%) vaccinees developed antibodies to Panama and 21/26 (80.8%) to Wyoming. None of these individuals suffered an influenza episode that season. The results suggest that the elderly might develop protective levels of cross-reactive A (H3N2) Wyoming HI antibodies following vaccination with the Panama strain. Such strains, like the ones included in the 2003-2004 influenza vaccine, might be expected to provide a broad-spectrum antibody response that could be effective even in the face of single season antigenic drift.     

Human sera possess a limited antibody repertoire to influenza neuraminidase antigenic variants selected in vitro

Four antigenic variants of the neuraminidase (NA) of A/Texas/77 (H3N2) virus were selected using monoclonal antibody at a frequency of one variant in 10(5) parental virions. The antigenic variants failed to react serologically with the monoclonal antibody used for their selection in vitro. The antigenic variants failed also to react serologically with a proportion of sera from children and adults although all of the sera reacted with the parental A/Texas/77 virus. Thus, certain human sera have a restricted antibody repertoire to influenza NA antigen which might enable virus antigenic variants to avoid anti-NA antibody-mediated neutralization in nature.     

Antibody against viruses in maternal and cord sera: specific antibody is concentrated on the fetal side of the circulation.

Paired maternal and cord sera from 100 pregnancies were tested for antibodies against herpes simplex virus, measles virus and respiratory syncytial virus by complement fixation and for antibodies against rubella virus, influenza A virus and influenza B virus by haemagglutination-inhibition. For four viruses (herpes simplex, measles, respiratory syncytial and rubella) higher levels of antibody were found in cord than in maternal sera. There was no difference between maternal and cord serum titres against influenza B virus but significantly higher levels of antibody against influenza A virus were found in maternal sera than in cord sera. This discrepancy was investigated by measuring antibodies against the surface antigens of influenza A by a complement fixation technique, and by single radial haemolysis. Both methods showed a preponderance of virus-specific antibody in cord sera. We conclude that IgG antibodies against most, if not all, viruses are concentrated on the fetal side of the circulation, but the conventional haemagglutination-inhibition techniques may fail to detect this difference.     

Human sera possess a limited antibody repertoire to influenza neuraminidase antigenic variants selected in vitro.

Four antigenic variants of the neuraminidase (NA) of A/Texas/77 (H3N2) virus were selected using monoclonal antibody at a frequency of one variant in 10(5) parental virions. The antigenic variants failed to react serologically with the monoclonal antibody used for their selection in vitro. The antigenic variants failed also to react serologically with a proportion of sera from children and adults although all of the sera reacted with the parental A/Texas/77 virus. Thus, certain human sera have a restricted antibody repertoire to influenza NA antigen which might enable virus antigenic variants to avoid anti-NA antibody-mediated neutralization in nature.     

Impact of swine influenza vaccine on serum antibody.

Comparison of a 1976 serum survey with one of 1977 has permitted an assessment of the impact of the national swine influenza vaccine program of 1976-1977 on the antibody status of the Michigan population. Prevalence of HI influenza virus antibody in premarital sera collected in 1976 prior to the vaccine program was compared to that in similar sera collected in 1977. Overall prevalence of A/New Jersey antibody (titers greater than or equal to 1:10) in 1976 sera was 22.3%. Little antibody was detected in sera from persons less than 40 years of age and prevalence peaked at age 50. Increased antibody prevalence was found for all age groups in sera collected in 1977 following the vaccine program, and the overall prevalence was 41.6%. Only 3.5% of those under 19 years of age were vaccinated, and post-vaccine prevalence for this group was 10%. This age group, comprising about 30% of the state population, appears to have had least exposure to swine influenza virus, and may be the population segment at greatest risk of infection should strains of this antigenic composition reappear. In contrast, highest prevalence of A/Victoria antibody was found in the 15 to 19 age group, where prevalence was 52%, compared to an overall prevalence at 40%.     

1996年广东省流感实验监测

1995年10月至1996年9月,广东省共分离到流感病毒46株,包括甲3型34株,甲1型2株,乙型10株。其中具“O”相特征的甲3型流感病毒23株。甲／广东／1／96、甲／广东／3／96的抗原性与往年甲3型的抗原性相比已发生明显的漂移。韶关市和海珠市两地的双相血清检测结果均证实为甲3型流感病毒感染,117份健康人群血清抗体检测结果,当年流行株甲／广东／1／96的抗体阳性率较低（58．97％）。因此甲3型为流行优势毒株,该型病毒抗原性漂移及人群抗体水平较低是造成流行的主要原因。     

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.     

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.     

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.     

Serum HI antibody and protection against influenza: a follow-up survey at community level of three epidemics caused by different H3N2-variants.

Serial blood specimens from Rh-negative pregnant women sent to laboratory for Rh antibody testing were stored and used for influenza investigations. The study period covered three epidemics, each caused by a different variant of influenza A (H3N2) virus. The relationship between pre-epidemic haemagglutination inhibiting (HI) antibody level against the epidemic virus and serological evidence of infection was analysed. Titre associated with protection was very similar in the three epidemics. In 1973-74 the influenza A epidemic had an exceptional course characterized by prolonged duration. The study revealed data on the rate of infection in one age and sex category that are difficult to obtain using standard indicators of influenza epidemiology.     

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.     

Neutralizing antibody but not hemagglutination antibody provides accurate evaluation for protective immune response to H5N1 avian influenza virus in vaccinated rabbits

In order to develop an animal model and an assay method to evaluate protective immune response to H5N1 avian influenza vaccination, H5N1 avian influenza vaccine was prepared. New Zealand rabbits were assigned to receive two doses of vaccine with different hemagglutinin (HA) dosage. The sera from vaccinated rabbits was evaluated to determine antibody titer and specificity using different tested methods including hemagglutination inhibition assay (HI), neutralizing assay (NT), cross-HI assay, cross-single immunodiffusion assay and cross-neutralization assay. The titer of HI antibody from rabbits immunized with different doses of HA were no less than 1:40 among groups 14 days after the first immunization. Whereas the NT antibody titer was less than 1:10 among groups 14 days after the first immunization. NT antibodies can be detected 14 days after the second immunization in rabbits immunized at HA doses higher than 6 μg, and the NT antibody titers were equal to or higher than 1:40. A good concentration-dependent NT antibody response can be detected in the vaccinated rabbits 14 days after the second immunization, and in contrast, no concentration-dependent relationship can be seen for HA antibody. The cross-HI test showed sera from vaccinated rabbits could cross react with influenza A H5N1 virus with the titers higher than 1:40. No cross reaction among different types (influenza A/H1N1 virus, influenza A/H3N2 virus, influenza B virus and influenza A/H5N1 virus) can be detected in the sera using the single immunodiffusion assay and using NT antibody test. This showed NT antibody test was demonstrated as a more accurate assay method for evaluating vaccination and quality of the vaccine than HI antibody test.