118
LETTERS to the EDITOR
Activity of influenza vaccine against virus strains now circulating SIR,-Influenza viruses are continually evolving, thus evading naturally acquired immunity by mutations in the haemagglutinin (HA) gene.’ As a result vaccines have to be updated every year to ensure that their antigenic composition reflects that of circulating strains. It is sometimes difficult to achieve this matching but this is the only way if influenza vaccines are to yield 70-80% protection in the especially vulnerable populations of the over-65s and patients with chronic respiratory, cardiovascular, and metabolic diseases. Influenza A (H3Nz) virus is currently active in the USA:2 the WHO Influenza Centre, US Centers for Disease Control (personal communication, Dr Nancy Cox) reports outbreaks since midOctober in schools in eight states, and influenza A viruses have been isolated in twenty-seven states. 325 influenza isolates have been reported, more than 99% being influenza A, predominantly H3Nz. These viruses are related to but not identical with A/Beijing/353/89, and we need to know if this vaccine strain protects against the current epidemic virus. In November we immunised 69 student volunteers aged between 18-27 at the London Hospital Medical College. They were given 0-5 ml Duphar trivalent sub-unit influenza vaccine intramuscularly (15 g HA of A/Beijing/353/89 [H3Nz], A/Taiwan/l/86 [H1N1], B/Yamagata/16/88). A smaller group of volunteers was immunised in Bergen, Norway, with the Pasteur Merieux split virus influenza vaccine (13-5 Ilg HA of A/Beijing/353/89 [H3Nz], A/Singapore/6/ 86 [H1N1], B/Yamagata/16/88). Blood samples were taken shortly before immunisation and 3 weeks later. Haemagglutination inhibition (HI) tests were used to compare levels of antibody to the homologous viruses in the vaccine and to the recently isolated strains in the community, including the first isolates of the new H3Nz variant in the UK (A!England/261/913) and epidemiologically relevant strains A/Victoria/36/88 (H1N1) and B/Panama/45/90. There have been 6 influenza A (H3Nz) isolates confirmed in England since September (personal communication, Dr Mina Chakraverty). Pre and post vaccination HI antibody titres against A/Beijing/ 353/89 and A/England/261/91 in the students immunised in London are as follows, a titre of 40 or more indicating protection:4
Strain
A.Bei)mg353’89 A, England
261 91
Sera with HI tltres
GMT
(pre/post)
(pre/post)
< 10
>_ 40
8,1
31/66
27-1/11922
131
27’61
221;’1019
12% had pre-existing antibody to the vaccine strain, nor did 19% to A ’England / 2 61/ 91. After vaccination there was a significant rise in HI antibody, and 96% and 88% of volunteers had protective HI titres to vaccine strain and to A/EngIand/261 ’91, respectively. Geometric mean antibody titres (GMT) against both influenza A (H3Nz) strains were high after immunisation. 88% and 97% of volunteers had protective HI antibody levels against the influenza A (H,N,) and influenza B components of the vaccine, respectively no
(data not shown). An effective immune response was also noted with the split vaccine (data not shown). Volunteers in Bergen had significant rises in antibody levels as early as 8 days after immunisation. Previous data on the rapidity of the immune response’ raise the question as to whether at-risk groups who have missed the normal schedule of
vaccination in the autumn could still be successfully vaccinated in the event of high influenza activity. Thus we can report an excellent serological response postvaccination to the H3N2 component of the vaccine and a good match between the current vaccine and a recent influenza A (H3N2) isolate from the UK. We thank Dr Mina Chakraverty for providing the UK isolate, Maurits Kok (Solvay-Duphar, Weesp, Netherlands) for assistance with the study, and the study volunteers. M. Z. is an MRC training fellow. Academic Virology, London Hospital Medical London E1 2AD, UK
National Institute of and Control, South Mimms
M. ZUCKERMAN College,
Biological Standards
Department of Microbiology and Immunology, University of Bergen, Bergen, Norway
R. COX J. OXFORD
J. TAYLOR J. WOOD
LARS HAAHEIM
1. Wiley DC, Skehel JJ. Structure and function of the haemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem 1987; 56: 365-94. 2. Anon. Wkly Epidemiol Rec Nov 29, 1991: 357. 3. Anon. Commun Dis Rep 1991, 1 (no 49). 6 4. Oxford JS, Schild GC. In: Collier LH, Timbury MC, eds. Topley & Wilson’s principles of bacteriology, virology and immunity. London: Edward Arnold, 1990: 291-322. 5 Zuckerman MA, Wood J, Chakraverty P, Taylor J, Heath AB, Oxford JS. Serological responses in volunteers to inactivated trivalent sub-unit influenza vaccine, antibody A and B strains and evidence of a rapid immune response. J Med Virol 1991; 33: 133-37.
Mood and
peak flow in asthma
SiR,—The correlation between mood and peak flow in patients with asthma is commonly assumed to be the result of mood change affecting peak flow via vagal nerve innervation.1 The alternative, that peak flow variation causes mood change, has been suggested recently.2 However, the direction of causality cannot be inferred from correlations based on non-interventionist studies. We have been studying the long-term stability of peak flow and mood in asthmatics and non-asthmatics by a diary method. Peak flow and mood (positive and negative affect schedule [pants]3) were measured twice daily. One of our volunteers believed herself to be non-asthmatic but her general practitioner diagnosed asthma and she started treatment half-way through the study. Treatment (inhaled salbutamol) resulted in a striking increase in peak flow. Thus, we had the opportunity of observing an ethical "experimental" manipulation in a real-life setting. If mood change drives peak flow variation, a change in peak flow consequent on therapy should not lead to an alteration in mood. On the other hand, if flow drives mood, an improvement in peak flow should be associated with an improvement in mood, which is what happened in this patient (figure). Before treatment the correlation between mood and peak expiratory flow rate (PEFR) over 35 days was 0 53 for morning and 0 56 for evening measures, consistent with the hypothesis2 that significant correlations are obtained only when asthma is poorly controlled. During the 18 days that salbutamol was progressively altering PEFR the correlations rose to 0-75 and 0 79, respectively. Although measurements were terminated at this point, we would expect the mood/PEFR
LETTERS to the EDITOR
Activity of influenza vaccine against virus strains now circulating SIR,-Influenza viruses are continually evolving, thus evading naturally acquired immunity by mutations in the haemagglutinin (HA) gene.’ As a result vaccines have to be updated every year to ensure that their antigenic composition reflects that of circulating strains. It is sometimes difficult to achieve this matching but this is the only way if influenza vaccines are to yield 70-80% protection in the especially vulnerable populations of the over-65s and patients with chronic respiratory, cardiovascular, and metabolic diseases. Influenza A (H3Nz) virus is currently active in the USA:2 the WHO Influenza Centre, US Centers for Disease Control (personal communication, Dr Nancy Cox) reports outbreaks since midOctober in schools in eight states, and influenza A viruses have been isolated in twenty-seven states. 325 influenza isolates have been reported, more than 99% being influenza A, predominantly H3Nz. These viruses are related to but not identical with A/Beijing/353/89, and we need to know if this vaccine strain protects against the current epidemic virus. In November we immunised 69 student volunteers aged between 18-27 at the London Hospital Medical College. They were given 0-5 ml Duphar trivalent sub-unit influenza vaccine intramuscularly (15 g HA of A/Beijing/353/89 [H3Nz], A/Taiwan/l/86 [H1N1], B/Yamagata/16/88). A smaller group of volunteers was immunised in Bergen, Norway, with the Pasteur Merieux split virus influenza vaccine (13-5 Ilg HA of A/Beijing/353/89 [H3Nz], A/Singapore/6/ 86 [H1N1], B/Yamagata/16/88). Blood samples were taken shortly before immunisation and 3 weeks later. Haemagglutination inhibition (HI) tests were used to compare levels of antibody to the homologous viruses in the vaccine and to the recently isolated strains in the community, including the first isolates of the new H3Nz variant in the UK (A!England/261/913) and epidemiologically relevant strains A/Victoria/36/88 (H1N1) and B/Panama/45/90. There have been 6 influenza A (H3Nz) isolates confirmed in England since September (personal communication, Dr Mina Chakraverty). Pre and post vaccination HI antibody titres against A/Beijing/ 353/89 and A/England/261/91 in the students immunised in London are as follows, a titre of 40 or more indicating protection:4
Strain
A.Bei)mg353’89 A, England
261 91
Sera with HI tltres
GMT
(pre/post)
(pre/post)
< 10
>_ 40
8,1
31/66
27-1/11922
131
27’61
221;’1019
12% had pre-existing antibody to the vaccine strain, nor did 19% to A ’England / 2 61/ 91. After vaccination there was a significant rise in HI antibody, and 96% and 88% of volunteers had protective HI titres to vaccine strain and to A/EngIand/261 ’91, respectively. Geometric mean antibody titres (GMT) against both influenza A (H3Nz) strains were high after immunisation. 88% and 97% of volunteers had protective HI antibody levels against the influenza A (H,N,) and influenza B components of the vaccine, respectively no
(data not shown). An effective immune response was also noted with the split vaccine (data not shown). Volunteers in Bergen had significant rises in antibody levels as early as 8 days after immunisation. Previous data on the rapidity of the immune response’ raise the question as to whether at-risk groups who have missed the normal schedule of
vaccination in the autumn could still be successfully vaccinated in the event of high influenza activity. Thus we can report an excellent serological response postvaccination to the H3N2 component of the vaccine and a good match between the current vaccine and a recent influenza A (H3N2) isolate from the UK. We thank Dr Mina Chakraverty for providing the UK isolate, Maurits Kok (Solvay-Duphar, Weesp, Netherlands) for assistance with the study, and the study volunteers. M. Z. is an MRC training fellow. Academic Virology, London Hospital Medical London E1 2AD, UK
National Institute of and Control, South Mimms
M. ZUCKERMAN College,
Biological Standards
Department of Microbiology and Immunology, University of Bergen, Bergen, Norway
R. COX J. OXFORD
J. TAYLOR J. WOOD
LARS HAAHEIM
1. Wiley DC, Skehel JJ. Structure and function of the haemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem 1987; 56: 365-94. 2. Anon. Wkly Epidemiol Rec Nov 29, 1991: 357. 3. Anon. Commun Dis Rep 1991, 1 (no 49). 6 4. Oxford JS, Schild GC. In: Collier LH, Timbury MC, eds. Topley & Wilson’s principles of bacteriology, virology and immunity. London: Edward Arnold, 1990: 291-322. 5 Zuckerman MA, Wood J, Chakraverty P, Taylor J, Heath AB, Oxford JS. Serological responses in volunteers to inactivated trivalent sub-unit influenza vaccine, antibody A and B strains and evidence of a rapid immune response. J Med Virol 1991; 33: 133-37.
Mood and
peak flow in asthma
SiR,—The correlation between mood and peak flow in patients with asthma is commonly assumed to be the result of mood change affecting peak flow via vagal nerve innervation.1 The alternative, that peak flow variation causes mood change, has been suggested recently.2 However, the direction of causality cannot be inferred from correlations based on non-interventionist studies. We have been studying the long-term stability of peak flow and mood in asthmatics and non-asthmatics by a diary method. Peak flow and mood (positive and negative affect schedule [pants]3) were measured twice daily. One of our volunteers believed herself to be non-asthmatic but her general practitioner diagnosed asthma and she started treatment half-way through the study. Treatment (inhaled salbutamol) resulted in a striking increase in peak flow. Thus, we had the opportunity of observing an ethical "experimental" manipulation in a real-life setting. If mood change drives peak flow variation, a change in peak flow consequent on therapy should not lead to an alteration in mood. On the other hand, if flow drives mood, an improvement in peak flow should be associated with an improvement in mood, which is what happened in this patient (figure). Before treatment the correlation between mood and peak expiratory flow rate (PEFR) over 35 days was 0 53 for morning and 0 56 for evening measures, consistent with the hypothesis2 that significant correlations are obtained only when asthma is poorly controlled. During the 18 days that salbutamol was progressively altering PEFR the correlations rose to 0-75 and 0 79, respectively. Although measurements were terminated at this point, we would expect the mood/PEFR
