tetano
Editor, Senior Moderator
The Lancet Infectious Diseases, Volume 14, Issue 2, Page 101, February 2014
doi:10.1016/S1473-3099(13)70698-4Cite or Link Using DOI
Copyright ? 2014 Elsevier Ltd All rights reserved.
Age and different influenza viruses
Masanori Terajima aEmail Address, Mary Dawn T Co a, Francis A Ennis a
We read with interest the Comment by Guus Rimmelzwaan and colleagues1 explaining the different age distribution of cases caused by avian influenza A viruses of the H5N1 and H7N9 subtypes. They proposed that the low incidence of severe H5N1 infections in elderly people compared with that in younger people might be related to the presence of cross-protective antibodies to neuraminidase that had been induced by seasonal influenza A H1N1 viruses. There is another type of cross-reactive antibody that might contribute to protection against the H5N1 subtype. By contrast with conventional neutralising antibodies binding to the globular head of the haemagglutinin, which are subtype-specific or even strain-specific, antibodies binding to the stalk region of the haemagglutinin are broadly neutralising. Some antibodies to the haemagglutinin stalk are subtype-cross-reactive.2
Previously, Smallman-Raynor and Cliff3 suggested the possibility that people born before 1969 have immunity to the H5N1 subtype, which might have been associated with geographically widespread influenza A events before the late 1960s. We proposed4 that widespread influenza A events before the late 1960s could have been attributable to the H2N2 pandemic starting in 1957, based on and expanding the hypothesis suggested by Palese and Wang.5 The stalk-specific neutralising antibodies induced against H2 subtype viruses in 1957?68 might be more cross-reactive to the H5 subtype than those induced against the H1 subtype (the H1, H2, and H5 subtypes belong to group 1 haemagglutinins, but the H5 subtype is more similar to the H2 subtype than to the H1 subtype). This cross-reactivity could have rendered the population born before 1968 more resistant to the H5N1 subtype than are people born after 1968, who have only been exposed to seasonal H1N1 and H3N2 subtypes.
Because the H7 subtype belongs to group 2 haemagglutinins, most stalk-specific neutralising antibodies induced against the H2 subtype are unlikely to be cross-reactive to the H7 subtype. Therefore, the older group might have no more resistance against the H7 subtype than do the younger age group, resulting in the more typical age distribution of H7N9 subtype as an infectious disease. Although the H3 subtype belongs to the same group 2 haemagglutinin as H7, in view of the fact that the H3 subtypes have been circulating since 1968, it is difficult to know the effect of antibodies generated against the H3 subtype on resistance against the H7 subtype. We think our hypothesis is not mutually exclusive with that offered by Rimmelzwaan and colleagues.
We were supported by the National Institutes of Health?National Institutes of Allergy and Infectious Diseases grant U19 Al-057319. We declare that we have no conflicts of interest.
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(13)70698-4/fulltext?rss=yes
doi:10.1016/S1473-3099(13)70698-4Cite or Link Using DOI
Copyright ? 2014 Elsevier Ltd All rights reserved.
Age and different influenza viruses
Masanori Terajima aEmail Address, Mary Dawn T Co a, Francis A Ennis a
We read with interest the Comment by Guus Rimmelzwaan and colleagues1 explaining the different age distribution of cases caused by avian influenza A viruses of the H5N1 and H7N9 subtypes. They proposed that the low incidence of severe H5N1 infections in elderly people compared with that in younger people might be related to the presence of cross-protective antibodies to neuraminidase that had been induced by seasonal influenza A H1N1 viruses. There is another type of cross-reactive antibody that might contribute to protection against the H5N1 subtype. By contrast with conventional neutralising antibodies binding to the globular head of the haemagglutinin, which are subtype-specific or even strain-specific, antibodies binding to the stalk region of the haemagglutinin are broadly neutralising. Some antibodies to the haemagglutinin stalk are subtype-cross-reactive.2
Previously, Smallman-Raynor and Cliff3 suggested the possibility that people born before 1969 have immunity to the H5N1 subtype, which might have been associated with geographically widespread influenza A events before the late 1960s. We proposed4 that widespread influenza A events before the late 1960s could have been attributable to the H2N2 pandemic starting in 1957, based on and expanding the hypothesis suggested by Palese and Wang.5 The stalk-specific neutralising antibodies induced against H2 subtype viruses in 1957?68 might be more cross-reactive to the H5 subtype than those induced against the H1 subtype (the H1, H2, and H5 subtypes belong to group 1 haemagglutinins, but the H5 subtype is more similar to the H2 subtype than to the H1 subtype). This cross-reactivity could have rendered the population born before 1968 more resistant to the H5N1 subtype than are people born after 1968, who have only been exposed to seasonal H1N1 and H3N2 subtypes.
Because the H7 subtype belongs to group 2 haemagglutinins, most stalk-specific neutralising antibodies induced against the H2 subtype are unlikely to be cross-reactive to the H7 subtype. Therefore, the older group might have no more resistance against the H7 subtype than do the younger age group, resulting in the more typical age distribution of H7N9 subtype as an infectious disease. Although the H3 subtype belongs to the same group 2 haemagglutinin as H7, in view of the fact that the H3 subtypes have been circulating since 1968, it is difficult to know the effect of antibodies generated against the H3 subtype on resistance against the H7 subtype. We think our hypothesis is not mutually exclusive with that offered by Rimmelzwaan and colleagues.
We were supported by the National Institutes of Health?National Institutes of Allergy and Infectious Diseases grant U19 Al-057319. We declare that we have no conflicts of interest.
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(13)70698-4/fulltext?rss=yes