Pratima Chakraverty

Genetic and antigenic variation in the haemagglutinin of recently circulating human influenza A (H3N2) viruses in the United Kingdom

SummaryVariation in the haemagglutinin (HA) gene of influenza A (H3N2) viruses isolated in the U. K. and abroad from 1992–1994, was determined by nucleotide sequencing of the HA1 domain of the HA gene. Viruses isolated in the U.K. early in the 1992–93 season were from the A/Beijing/353/89 lineage and were replaced later that season by viruses from the A/Beijing/32/92 lineage. Viruses from the new lineage continued to be isolated during the 1993–94 season, but were heterogeneous. Most of these isolates were more closely related to an A/Beijing/32/92 variant, A Hong Kong/23/92, but could be distinguished into three groups by serology (of which one group was circulating during the previous season) and four groups based on sequence variation in the HA gene. However, phylogenetic analysis of antigenically-distinct isolates showed that the HA gene is evolving along one lineage. Sequence analysis identified mainstream, subgroup and strain specific amino acid substitutions. There was a broad correlation between the observed amino acid changes and the antigenic sites of the HA. The results of this study highlight the value of regular molecular analysis of circulating viruses.

Prevalence of Antibody to Current Influenza Viruses and Effect of Vaccination on Antibody Response

The extent of antibody to the influenza virus A/Hong Kong/68 (H3N2) after four years of prevalence was investigated in Britain and in the U.S.A. The results indicated a high incidence in both populations. The prevalence of antibody to a variant A/England/42/72 (H3N2) which has been causing epidemics of influenza in the southern hemisphere during the middle months of 1972 was also investigated. The differences reflect the shift in antigenic content of this variant, and although the overall proportion of the sera with antibody at > 1/40 was 37%, some age groups had an incidence of only 20% or less with antibody at this level. A commercial inactivated A/Hong Kong/68 influenza vaccine was given to a group of volunteers in Britain to see how effective it might be in stimulating antibody to the variant A/England/42/72. The antibody responses were better than expected from earlier vaccine studies, and 63% of the vaccinees developed antibody to the A/England/42/72 to levels thought likely to be protective. This suggested that until a vaccine made with the variant A/England/42/72 becomes available the present A/Hong Kong/68 vaccine would be of use to protect those at special risk this winter.

Antigenic relationship between influenza C viruses.

SummaryThe object of this study was to determine whether antigenic groupings exist among influenza C viruses. Altogether seven influenza type C strains were examined by reciprocal haemagglutination-inhibition and serum neutralization tests with sera produced in ferrets. Some biological properties were also compared and differences were found in their ability to agglutinate erythrocytes from various species, in their ability to adsorb onto rat and fowl erythrocytes, and in their rates of elution from the cells.The results obtained using these techniques confirmed that antigenic variation exists among influenza C viruses although it is not as clear cut as among influenza A viruses. This was supported by the results of a serological survey of antibody in different age groups.

Antigenic Variants of Influenza B Virus

From 1967 to 1971 little antigenic variation was detected in the prevalent influenza B viruses but in December 1972 a new antigenic variant of influenza B was isolated in Hong Kong from sporadic cases of influenza. The new variant, B/Hong Kong/5/72, possessed a haemagglutinin antigen which showed considerable antigenic differences from that of former influenza B strains while its neuraminidase antigen was closely related to that of the earlier, 1967-71, isolates. The B/Hong Kong/5/72 variant became the predominant influenza B strain in the United Kingdom by early summer 1973, and in both the United Kingdom and Japan this strain was associated with outbreaks of influenza. Strains antigenically intermediate between the 1967-71 isolates and B/Hong Kong/5/72 were isolated in a number of countries, often concurrently with B/Hong Kong/5/72-like strains. Serological studies indicated that antibody to B/Hong Kong/5/72 was infrequent in the populations in the United Kingdom and the U.S.A., suggesting the possibility of future epidemic activity associated with the new variant. In addition, conventional inactivated influenza vaccines containing the older influenza B isolates given to volunteers stimulated poor antibody responses to B/Hong Kong/5/72 virus. These studies indicate the desirability of immunizing high risk patients against B/Hong Kong/5/72-like viruses before the coming influenza season. Vaccine containing the new variant influenza B strain are currently available in the United Kingdom.

Comparison of haemagglutination-inhibition and single-radial-haemolysis techniques for detection of antibodies to influenza B virus.

SummarySome of the strains influenza B isolated between 1975 to 1978 showed a significant drift away from the prototype strain B/HK/8/73 when tested by cross haemagglutination-inhibition.A serum survey for antibody to two strains of influenza B virus was carried out comparing haemagglutination-inhibition (HI) and single-radial haemolysis (SRH) tests. The SRH technique was found to be more sensitive than the HI test.

Influenza in the United Kingdom 1982-85.

Influenza surveillance in the UK between the years 1982 and 1985 has demonstrated the regular winter appearance of influenza A virus of both H1N1 and H3N2 subtypes and influenza B. Their antigenic diversity is described and correlated with the national statistics for morbidity and mortality for influenza. One unexpected finding has been that despite the wide circulation of influenza viruses there has been a continuation of winters without significant increases in influenza deaths or morbidity. A previous report of influenza surveillance (Pereira & Chakraverty, 1982) noted an already unusual series of three consecutive winters with this pattern. This report records a further 4 years bringing a total of seven successive winters without evidence of epidemics of severe disease associated with influenza viruses, as indicated by the national UK statistics.

Influenza in the United Kingdom 1977–1981

The laboratory surveillance of influenza in the UK has continued to demonstrate the regularity of influenza outbreaks each winter even in the absence of increase in the other indices which reflect the morbidity and mortality associated with influenza. The period of five years from 1976 to 1981 has seen the appearance of a second sub-type of influenza. A with the return of the historic H1N1 virus; and the continued circulation of H3N2 concurrently with H1N1 virus. Variants of both these influenza A viruses have been demonstrated as well as further changes in the strains of influenza B virus isolated during this time.

The laboratory surveillance of influenza epidemics in the United Kingdom 1968-1976.

The extensive laboratory investigations of respiratory disease in the U.K. over many years have demonstrated the frequency with which influenza viruses, both A and B, are found each winter. Only rarely are none isolated. These findings correlate well with other indicators of influenza such as increases in sickness benefit claims and in deaths attributed to influenza and pneumonia. However, outside these demonstrable peaks of incidence influenza viruses have been found to circulate over considerably longer periods often first appearing as early as November and continuing through to April or even May. But there has been no regular or predictable pattern determined. The period of 1968-76 has seen a series of differently developing influenza winter epidemics caused by a series of the H3N2 virus. The contributions of virus isolation and serology to influenza surveillance is discussed.

Hong Kong influenza in the Royal Air Force 1968–70

A prospective serological and clinical study of the epidemics due to the A2/Hong Kong/68 influenza virus was made during the winters 1968-9 and 1969-70 in volunteer subjects in the Royal Air Force. In October 1968 nearly all subjects had haemagglutination inhibiting (HI) antibody to the A2/Singapore/57 virus and more than half had antibody to strains more recently prevalent in Britain. The proportion with HI antibody to A2/Hong Kong/68 increased from 31% in October 1968 (most at low titres) to 44% after the first epidemic and 72% after the second (most at high titres). Serological infection rates were much lower in those who had detectable antibody at the beginning of each winter than in those who did not. Respiratory illnesses coupled with serological evidence of influenza infection during the winter were rare in persons with an initial titre of HI antibody of 1/40 or more. Infection in the first winter conferred complete protection against infection, with or without illness, in the second. In both epidemics about half those with serological evidence of infection had no reported illness.

The influence of antigenic variation on influenza A2 epidemics

The pattern of epidemics due to influenza A 2 virus can be determined by several means: by following changes in sickness benefit claims, mortality rates and general practitioner consultation rates (Miller & Lee, 1969) and by accumulating laboratory evidence of the presence of influenza viruses in the population. Over the past decade information from these various sources has been found to correlate very closely and a clear picture can be drawn of the epidemics which have occurred every winter but three since 1957. The factors which allow such epidemics to develop are only partly understood but there are two which can be measured and which certainly play a part. One of these is the antigenic structure of the prevalent virus and the other is the antibody directed against it in the exposed population. Both these factors are unstable because of the antigenic variation which influenza A virus undergoes from time to time and because serum antibody is not necessarily maintained at high titre against the original infecting strain and, indeed, may become undetectable against a sufficiently changed new variant. Attempts have been made to assess the importance of these factors in explaining the repeated epidemics due to influenza A2 virus which have occurred in Britain since 1957.