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.     

Antibody responses of swine to type A influenza viruses during the past ten years in Japan

A total of 6346 swine sera collected at an abattoir in the city of Obihiro, Hokkaido during the years 1978-87 were tested for the presence of antibodies to swine and human influenza viruses. A high incidence of antibody to A/New Jersey/8/76 (swine type H1N1) virus was observed throughout the 10 years except for the occasional month and a single long period of 15 months. Antibodies to human H3N2 virus in swine appeared to be related to the epidemics of human influenza which occurred in the study area during the years 1980-3, but unrelated to the epidemics during the years 1984-7. A large number of swine were found to be antibody positive to a human H1N1 virus during the period April to June 1964, and a smaller number, during the period November 1986 to June 1987. Both were in relation to human influenza epidemics. However, there were long periods where human H1N1 antibodies in swine could not be found.     

Antibody response to immunization with influenza A/USSR/77 (H1N1) virus in young individuals primed or unprimed for A/New Jersey/76 (H1N1) virus.

A group of 269 pupils of the Harbour and Transport Training Institute in Rotterdam (group A), aged 13-20 years, and of 109 patients of the Dr Mr Willem van den Bergh Foundation at Noordwijk (group B), aged 11-21 years, were immunized with a whole virus vaccine containing 10, 20, or 40 microgram HA of A/USSR/92/77 (H1N1) influenza virus. A booster vaccination was administered 6 weeks later with 20 microgram HA of the same virus. Many of the participants had been immunized during the two preceding years with a whole virus vaccine containing A/New Jersey/8/76 (H1N1) (A/NJ/76) virus. The side-effects, mostly of a moderate nature, increased with the dose of virus in the vaccine. In group A side effects were least frequent in the vaccinees who had never received A/NJ/76 vaccine. A single dose of A/USSR/77 vaccine did not produce satisfactory levels of homologous antibodies. After booster immunization with 20 microgram HA of A/USSR/77 virus participants showed a higher homologous antibody response in all vaccine-dose groups if they had not been immunized with A/NJ/76 virus in previous years. After primary and especially after booster immunization with A/USSR/77 virus, a very high response against A/NJ/76 virus and adequate levels of A/NJ/76 antibody were found in participants who had been immunized previously with A/NJ/76 virus. Those who had not been immunized with this virus previously showed no or a very low antibody response to A/NJ/76 virus.     

An investigation of antigenic drift of neuraminidases of influenza A (H1N1) viruses

A newly developed lectin neuraminidase test (LNT) and a panel of mouse monoclonal and post-infection ferret antibodies have been used to analyse antigenic drift in N1 neuraminidases of influenza A viruses isolated between 1933 and 1957 and also between 1977 and 1980. Significant antigenic differences were detected among the 'early' (1933-57) viruses since the NA of viruses isolated one year apart could be distinguished serologically. The NA of the 're-emerged' virus A/USSR/92/77 (H1N1) was antigenically related but not identical to influenza A viruses isolated in 1949 (A/Paris/49 (H1N1), A/Geneva/49 (H1N1) which thus predates the previously observed antigenic similarity of A/USSR/77 with A/FW/50 (H1N1) virus.     

Infection with influenza A H1N1. 1. Production and persistence of antibody

Three outbreaks of influenza caused by influenza A H1N1 occurred in a boys' boarding school in 1978, 1979 and 1983. The serological response to infection with variants of the H1N1 virus was studied by radial haemolysis and haemagglutination inhibition after primary infection and reinfection. The persistence of this antibody was also studied. Infection in 1978 resulted in the production of persistent antibody to both the haemagglutinin and neuraminidase of the homotypic strain. Antibody which cross-reacted with later variants of the virus was less frequently produced, the peak response was delayed and such antibody persisted less well. Infection in 1979 resulted in a similar response to that observed in 1978 after primary infection. Reinfection resulted in a broad response in all cases. In 1983 all infected boys produced antibody which reacted with the homotypic strain but only approximately one-third of primary infections produced antibody which reacted with the A/USSR/92/77 strain. The neuraminidase of the A/USSR strain failed to detect one third of the primary infections. Reinfection again resulted in a broad response.     

Infection with influenza A H1N1. 1. Production and persistence of antibody.

Three outbreaks of influenza caused by influenza A H1N1 occurred in a boys'' boarding school in 1978, 1979 and 1983. The serological response to infection with variants of the H1N1 virus was studied by radial haemolysis and haemagglutination inhibition after primary infection and reinfection. The persistence of this antibody was also studied. Infection in 1978 resulted in the production of persistent antibody to both the haemagglutinin and neuraminidase of the homotypic strain. Antibody which cross-reacted with later variants of the virus was less frequently produced, the peak response was delayed and such antibody persisted less well. Infection in 1979 resulted in a similar response to that observed in 1978 after primary infection. Reinfection resulted in a broad response in all cases. In 1983 all infected boys produced antibody which reacted with the homotypic strain but only approximately one-third of primary infections produced antibody which reacted with the A/USSR/92/77 strain. The neuraminidase of the A/USSR strain failed to detect one third of the primary infections. Reinfection again resulted in a broad response.     

An investigation of antigenic drift of neuraminidases of influenza A (H1N1) viruses.

A newly developed lectin neuraminidase test (LNT) and a panel of mouse monoclonal and post-infection ferret antibodies have been used to analyse antigenic drift in N1 neuraminidases of influenza A viruses isolated between 1933 and 1957 and also between 1977 and 1980. Significant antigenic differences were detected among the ''early'' (1933-57) viruses since the NA of viruses isolated one year apart could be distinguished serologically. The NA of the ''re-emerged'' virus A/USSR/92/77 (H1N1) was antigenically related but not identical to influenza A viruses isolated in 1949 (A/Paris/49 (H1N1), A/Geneva/49 (H1N1) which thus predates the previously observed antigenic similarity of A/USSR/77 with A/FW/50 (H1N1) virus.     

Efficacy of vaccination of pigs with different H1N1 swine influenza viruses using a recent challenge strain and different parameters of protection

This study investigates whether antigenic evolution within H1N1 swine influenza viruses can compromise vaccine efficacy and, specifically, whether the A/New Jersey/8/76 strain in the commercial swine influenza vaccines needs to be updated. Pigs were vaccinated twice intramuscularly with experimental monovalent vaccines derived from different H1N1 strains (A/New Jersey/8/76, Sw/Belgium/1/83 or Sw/Belgium/1/98) or with a commercial bivalent vaccine based on A/New Jersey/8/76 (H1N1) and A/Port Chalmers/1/73 (H3N2). Experimental and commercial vaccines contained a different adjuvant. Two weeks after the second vaccination, all pigs were challenged intratracheally with Sw/Belgium/1/98. Mean pre-challenge haemagglutination inhibition (HI) antibody titres against the challenge virus were lower for the experimental A/New Jersey/8/76 vaccine than for the other vaccines. The reduction in mean virus titres in the lungs was highly significant for the latter vaccines, including the commercial New Jersey-derived vaccine, but not for the experimental A/New Jersey/8/76 vaccine. Clinical signs after challenge were negligible in all vaccinates. Post-challenge levels of interferon-alpha and tumor necrosis factor-alpha in bronchoalveolar lavage fluids were reduced in the vaccinates, while levels of interleukin-1 and neutrophils were less consistent. Though the A/New Jersey/8/76 strain is less effective in preventing infection by Sw/Belgium/1/98 than the homologous virus or than Sw/Belgium/1/83, all strains can protect completely if antibody titres against the challenge virus are sufficiently high. Apart from the vaccine strain, adjuvant and antigenic dose may play a crucial role in vaccine efficacy.     

Serological studies of influenza viruses in pigs in Great Britain 1991-2.

Samples from a sow serum bank representative of the pig population of Great Britain collected during 1991-2, were examined for antibodies to influenza A, B and C viruses, using viruses which had been isolated from a variety of hosts. For influenza A viruses there was evidence of the continued circulation of classical swine H1N1 virus (26%) seroprevalence), and human H3N2 viruses (39%) which are antigenically most closely-related to A/Port Chalmers/1/73 virus. In addition antibodies were detected to A/swine/England/201635/92 (8%), a strain of H3N2 virus which appears to have arisen by antigenic drift from conventional H3N2 swine strains. Specific antibodies (2%) were detected to an H1N1 virus (A/swine/England/195852/92) related most closely to avian H1N1 strains. In tests with human H1N1 and H3N2 viruses, excluding isolates from pigs, the highest seroprevalence was detected to the prevailing strains from the human population. Serological tests with avian H4 and H10, human H2, equine 1 and 2 influenza A viruses were all negative. Seven pigs seropositive by haemagglutination-inhibition, virus neutralization and immunoblotting assays for antibody to influenza B virus, were randomly distributed geographically suggesting that influenza B viruses may be transmitted to pigs but fail to spread. The seroprevalence to influenza C viruses was 9.9% indicating that these viruses are widespread in pigs. These results provide further evidence that the pig can be infected by a number of influenza viruses, some of which may have significance in the epidemiology of human influenza.     

Recycling of H1N1 influenza A virus in man--a haemagglutinin antibody study.

Sera from people born between 1883 and 1930 and collected in 1977 were tested for the presence of HI antibodies to A/FM/1/47 (H1N1) virus and three recently (1977 and 1978) isolated influenza A-H1N1 viruses. The highest frequency of high-titred antibody to the four H1N1 viruses was detected in sera from people born in 1903-4, i.e. 42, 54, 38, and 22% had antibody against A/FM/1/47, A/Hong Kong/117/77, A/Brazil/11/78, and A/Fukushima/103/78 respectively. The birthdate groups 1896-1907 showed a higher percentage of HI antibody titres greater than or equal to 18, greater than or equal to 50, greater than or equal to 100 or greater than or equal to 1600 against the four H1N1 viruses than the birthdate groups 1907-30. This indicates the existence of an era, 1908-18, in which, apart from the H3N2 virus (1900-18), the H1N1 virus was epidemic among the human population.     

A comparison of live and inactivated influenza A (H1N1) virus vaccines. 1. Short-term immunity.

Groups of volunteers were immunized subcutaneously with one of three inactivated influenza virus A/USSR/77 (H1N1) vaccine preparations; a whole virus vaccine, a surface-antigen subunit adsorbed vaccine, or an aqueous surface-antigen subunit vaccine. The reactions to immunization were recorded, and the antibody response was measured 1 month later. A fourth group of volunteers were inoculated intranasally with live attentuated A/USSR/77 (H1N1) influenza virus; the reactions and antibody response of these volunteers were also measured. One month after immunization, the incidence of infection by challenge with homologous live attentuated virus was determined for all groups of volunteers. The results showed that all four vaccines used were relatively non-reactogenic, and that inactivated vaccines induced higher titres of serum antibody than the live attenuated vaccine. All the vaccines induced significant protection against challenge virus infection which was directly related to the level of serum HI antibody response.     

Sero-epizootiological study on swine influenza in a prefecture of Japan.

A total of 1799 swine sera collected in Toyama prefecture in the central part of Japan during the years 1978-82 were tested for antibody against swine influenza virus (SIV), A/New Jersey/8/76 (H1N1). A high prevalence of antibody was observed in the years after the severe epizootic of SI, 34.5% in 1979 and 51.7% in 1982. In other years, the percentages of positive sera were low and ranged from 1.7 to 12.4%. Regional variations were seen in relation to a small scale epizootic. No antibody to SIV was detected in any of the sera collected during the warm season. In the following dry and cold winter, however, a severe epizootic occurred among the swine populations.     

Comparison of influenza viruses isolated from man and from whales.

Four isolates of influenza virus strains from Moscow and Habarovsk that caused outbreaks of influenza in November and December 1977 in several cities of the USSR were studied and their haemagglutinins and neuraminidases were compared with those of other human and animal influenza viruses including A/whale/Pacific Ocean/76. In H1 tests these isolates, designated A/USSR/77, reacted with immune serum against A/FM/1/47 (H1N1) to the homologous titre, and with antiserum against A/whale/PO/19/76 virus to 1/8 of the homologous titre. In neuraminidase inhibition tests all A/USSR/77 isolates showed the presence of human N1 type neuraminidase, more closely related to A/sw/New Jersey/76 (Hsw1N1) than to A/FM/1/47 (H1N1) virus. The haemagglutinin of A/whale/Pacific Ocean/19/76 virus occupies an intermediate position between H0 and H1, but its neuraminidase is close to Nav2. The virus from whales multiplies better at low (28°C) and at high (40°C) temperatures than do the viruses of human origin that were tested.     

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.     

Haemagglutination-inhibition antibodies against influenza A and influenza B in maternal and neonatal sera.

Haemagglutination inhibition (HI) antibodies against the influenza viruses A/Hong Kong/8/68 (H3N2) and B/Nederland/77/66 were determined in 420 paired sera from mothers and newborns (umbilical cord sera), sampled in 1970-1. A higher concentration of antibodies against influenza A virus was found more frequently in neonatal than in maternal sera. By contrast, low titres against influenza B virus were more frequently observed in neonatal than in maternal sera. Maternal age, duration of pregnancy, and birth-weight did not affect the results of the tests. It is suggested that the titre of the newborn against an epidemic influenza virus can be predicted from that of the mother. Furthermore, the maternal titre may be an indication of the susceptibility of the newborn infant to influenza infections.     

Results of a two-year study of humoral immunity to influenza A and B viruses in children under the age of 14 years in Moscow and its suburbs

A serological survey of antibodies to influenza A(H1N1), A(H2N2), A(H3N2) and B viruses was done with sera collected in Moscow in October 1980 and November 1981 from 542 children under 14 years of age. The results of the study showed convincingly that influenza A(H2N2) viruses were not circulating in Moscow in 1980-81. Low titres found in the sera from four young children were due to cross-reactions which were eliminated from the sera by absorption with A/USSR/174/79(H3N2) virus. Low-level HI titres with A(H0N1) virus in 11 sera were not confirmed by single radial haemolysis (SRH).     

Haemagglutination-inhibition antibodies against influenza A and influenza B in maternal and neonatal sera

Haemagglutination inhibition (HI) antibodies against the influenza viruses A/Hong Kong/8/68 (H3N2) and B/Nederland/77/66 were determined in 420 paired sera from mothers and newborns (umbilical cord sera), sampled in 1970-1. A higher concentration of antibodies against influenza A virus was found more frequently in neonatal than in maternal sera. By contrast, low titres against influenza B virus were more frequently observed in neonatal than in maternal sera. Maternal age, duration of pregnancy, and birth-weight did not affect the results of the tests. It is suggested that the titre of the newborn against an epidemic influenza virus can be predicted from that of the mother. Furthermore, the maternal titre may be an indication of the susceptibility of the newborn infant to influenza infections.     

A comparison of live and inactivated influenza A (H1N1) virus vaccines. 2. Long-term immunity.

Groups of volunteers were immunized with one of three influenza virus vaccines, and the resistance to challenge infection with attenuated influenza A (H1N1) virus was measured 8 months later. The vaccines were aqueous subunit influenza A/USSR/77 (H1N1) vaccine, aqueous subunit influenza B/Hong Kong/73 vaccine, or attenuated influenza virus A (H1N1) vaccine. The B virus vaccine was included as a control to assess the incidence of natural A virus infection during the study period. A proportion of the B virus vaccinees had pre-existing A (H1N1) virus antibody and were used to study the immunity conferred by natural infection to the live virus challenge. The serum antibody responses were measured at 1 and 8 months after immunization. The results showed that all the vaccines induced serum HI antibody in a proportion of the volunteers; however, after 1 month, higher titres of serum antibody were found in volunteers given inactivated A vaccine than in those given live attenuated A virus vaccine. Eight months post-immunization the titres of serum antibody in volunteers given inactivated vaccine had declined significantly, but there were no changes in the antibody titres of those given live virus vaccine. The incidence of infection by the challenge virus at 8 months post-immunization was directly related to the serum antibody titres 1 month post-immunization; no evidence was obtained to suggest that those given live virus vaccine had a more solid immunity than those given inactivated vaccine.     

1997年秋1998年春军队人群流感病毒抗体检测分析

目的监测军队人群流感病毒抗体水平,获知易感人群的比例,了解流感毒株的变异幅度及流行趋势.方法1997年秋和1998年春2次共采集954例军人血清,应用近4年8种国内及国际流感病毒代表株,以微量半加敏血凝抑制方法进行了抗体检测.结果军队人群中甲3亚型流感病毒抗体水平较高,A/山东/9/93(H3N2)、A/汉防/359/95(H3N2)抗体阳性率为89%～77%,抗体平均滴度(GMT)最高达58.该人群对近年来4种不同甲1亚型毒株的抗体水平存在很大差异.A/桂防/10/94(H1N1)抗体阳性率为84%(97秋)和89%(98春),GMT分别为90和134;最新国内代表株A/京防/53/97(H1N1)抗体阳性率明显偏低,为18%(97秋)和30%(98春),GMT分别为25和33.军队人群对乙型流感的抵抗力始终偏低,其B/京防/184/93、B/深防/12/97抗体阳性率为41%～55%,GMT为27～35.结论该部队人群甲3亚型株抗体已达饱和水平,提示抗原可能会发生变异,在一些地区引起流感中度流行甚或出现新亚型而引起大规模流行.H1N1毒株可能在军营中引起局部流行,对此应加强预测预报工作.     

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.