Los días 7 y 8 de mayo organizamos en la Fundación Ramón Areces con la Fundación General CSIC el Simposio Internacional 'Microbiología: transmisión'. La "transmisión" en microbiología hace referencia al proceso por el que material genético es transferido de una célula a otra, de una población a otra. Es un proceso clave para entender el origen y la evolución de los seres vivos. El objetivo de esta reunión era conocer mejor la logística de la transmisión para ser capaces de modular o suprimir algunos procesos de transmisión dañinos.

1. Vaccinating against moving targets to stop transmission:
The case of seasonal influenza virus vaccines
Derek Smith
Cambridge University, UK

2. Introduction
Antigenic evolution
Evolution predictable?
Immune pressure to evolve
Pre-emptive vaccine updates

3. Cross-species transmission

4. Spanish flu
(H1N1)
Asian flu
(H2N2)
HongKong flu
(H3N2)
1918
1957
1968
Pandemic and Epidemic Influenza

5. Pandemic and Epidemic Influenza
Spanish flu
(H1N1)
1918
Asian flu
(H2N2)
1957
HongKong flu
(H3N2)
1968

6. Pandemic and Epidemic Influenza
Spanish flu
(H1N1)
1918
Asian flu
(H2N2)
1957
HongKong flu
(H3N2)
1968

7. Influenza virus

8. WHO global influenza surveillance
Epidemiological
Genetic
Antigenic Raw tabular data
qualitative interpretation only
paradoxes in data

9. Genetic data
BI/15793/68 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/16190/68 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/16398/68 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
HK/1/68 CAAGACCTTCCCGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/808/69 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/908/69 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGTCTGGGACATCATGCGG
BI/17938/69 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/93/70 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/2668/70 CAAGACCTTCCAGGAAATGACAACAGTACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/6449/71 CAAGACCTTCCAGGAAATGAAAACAGCACAGCAACGCTGTGCCTGGGACATCATGCAG
BI/21438/71 CAAGACCTTCCAGGAAATGACAAAAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/21801/71 CAAGACCTTCCAGGAAATGACAAAAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
HK/107/71 CAAGACCTTCCAGGAAATGACAACAGCAAAGCAACGCTGTGCCTGGGACATCATGCGG
BI/6022/72 CAAGACCTTCCAGGAAATGACAAAAGCACAGCAACGCTGTGCCTGGGACACCATGCAG
BI/21793/72 CAAGATTTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/23290/72 CAAGACTTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/23337/72 CAAGATTTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/23488/72 CAAGACTTTCCAGGGAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
EN/42/72 CAAGATCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/552/73 CAAGATTTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/748/73 CAAGACTTTCCAGGGAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/3517/73 CAAGACTTTCCAGGGAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
PC/1/73 CAAGACTTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/5146/74 CAAAACTTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/5930/74 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/5931/74 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/7398/74 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/9459/74 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/2600/75 CAAGACTTTCCAAGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
BI/2813/75 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCGG
VI/3/75 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACTCTGTGCCTGGGACATCATGCGG
BI/628/76 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCAG
BI/1761/76 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACTCTGTGCCTGGGACATCATGCGG
BI/1905/76 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACTCTGTGCCTGGGACATCATGCGG
BI/2271/76 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACGCTGTGCCTGGGACATCATGCAG
BI/5029/76 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACTCTGTGCCTGGGACATCATGCGG
BI/5657/76 CAAGACCTTCCAGGAAATGACAACAGCACAGCAACTCTGTGCCTGGGACATCATGCGG

10. CDC
Paradoxes, multiple labs, 5000

11. Introduction
Antigenic evolution
Evolution predictable?
Immune pressure to evolve
Pre-emptive vaccine updates

12. Pandemic and Epidemic Influenza
Spanish flu
(H1N1)
1918
Asian flu
(H2N2)
1957
HongKong flu
(H3N2)
1968

13. Spanish flu
(H1N1)
Asian flu
(H2N2)
HongKong flu
(H3N2)
1918
1957
1968
Pandemic and Epidemic Influenza

14. Antigenic map
Influenza A (H3N2) 1968-2004
Smith et al Science 305, 371-376, 2004.

15. Antigenic map
Influenza A (H3N2) 1968-2004
Smith et al Science 305, 371-376, 2004.

16. Antigenic map
Influenza A (H3N2) 1968-2004
Smith et al Science 305, 371-376, 2004.

17. Antigenic map
Influenza A (H3N2) 1968-2004
Smith et al Science 305, 371-376, 2004.

18. What next?

19. WHO Global Influenza Programme: Vaccine Recommendations
GLOBAL
HEALTH
SECURITY
text
Fujian-California cluster transition

20. WHO Global Influenza Programme: Vaccine Recommendations
GLOBAL
HEALTH
SECURITY
text
Locations
Atlanta
Melbourne
Tokyo
Cambridge
LondonSasha Klimov
Rabecca Garten
Xiyan Xu
Michael Shaw
Nancy Cox
Wenqing Zhang
Keiji Fukuda
Rod Daniels
Yi-Pu Lin
Vicky Gregory
Alan Hay
John McCauley
Takato Odagiri
Masatsugu Obuchi
Tsutomo Kageyama
Masato Tashiro
Ian Barr
Aeron Hurt
Naomi Komadina
Alan Hampson
Ian Gust
Anne Kelso
World Health Organization
Eugene Skepner
Colin Russell
Ron Fouchier
Derek Smith
Beijing
Dayan Wang
Yuelong Shu

21. CORE SURVEILLANCE BY THE FOLLOWING WHO NATIONAL INFLUENZA CENTERS
Albania Dr Alma Robo
Algeria Dr Fawzi DERRAR
Argentina Dr Vilma Savy
Dr Jorge Camara
Dr Osvaldo Uez
Australia Dr David Smith
Dr Chris Birch
Dr Dominic Dwyer
Austria Prof. Dr. Therese Popow-Kraupp
Prof. Dr. Franz X. Heinz
Bangladesh Dr S. Begum
Belgium Dr Fernande Yane
Brazil Dr Terezinha Maria de Paiva
Dr Wyller Alencar de Mello
Dr Marilda Siqueira
Bulgaria Dr Rositsa Kotseva
Canada Dr Yan Li
Chile Dr Rodrigo Fasce
China Dr Yuelong Shu
China, Hong
Kong SAR
Dr Wilina Lim
Colombia Dr Gloria J. Rey
Costa Rica Dr Jenny Lara
Czech Republic Dr Martina Havlickova
Denmark Dr Lars Peter Nielsen
Ecuador Dr A. Alva
Egypt Dr Mostafa Orkhan
El Salvador Ms Celina de Lozano
Fiji Islands Dr Josefa Koroivueta
Finland Dr Reijo Pyhala
France Dr Martine Valette
France Dr Sylvie Van der Werf
French Guiana Dr Jacques Morvan
New Caledonia Dr Alain Berlioz-Arthaud
Germany Dr Brunhilde Schweiger
Dr Rolf Heckler
Greece Dr Andreas Mentis
Dr Vassiliki Kyriazopoulou-Dalaina
Honduras Dr J. R. Pereira
Hungary Dr I. Jankovics
Iceland Dr Arthur Löve
India Dr A.C. Mishra
Dr Usha Soren Singh
Dr Ranjana Deshmukh
Indonesia Dr. Endang R. Sedyaningsih, DrPH
Iran Dr Talaat Azad
Dr W. Hall
Israel Dr Yael Shalev
Italy Dr Dr Isabella Donatelli
Jamaica Dr Saudra Jackson
Japan Dr Masato Tashiro
Kazakhstan Dr A. Ismagulov
Kuwait Dr S. Al-Mufti
Latvia Dr Vaira-Irisa Kalnina
Madagascar Dr Dominique Rousset
Malaysia Dr S. Mangalam
Malaysia Dr Shamala Devi
Mexico Dr Irma Lopez Martinez
Mongolia Dr D. Mend-saikhan
Morocco Dr Rajae Aouad
Netherlands Dr Albert D. M. E. Osterhaus
New Caledonia Dr Alain Berlioz-Arthaud
New Zealand Dr Sue Huang
New Zealand Dr M. Croxson
Norway Dr Olav Hungnes
Panama Dr Jorge Motta
Paraguay Dr Julio Manzur
Peru Dr Yvonne Torres de Yon
Philippines Dr Fem Julia Paladin
Poland Dr Lidia Brydak
Portugal Dr Helena Rebelo de Andrade
Republic of
Korea
Dr Chun Kang
Romania Dr Costin Cernescu
Dr Viorel Alexandrescu
Dr C. Apetrei
Russian Fed. Prof. Dmitry K. Lvov
Prof. Oleg I. Kiselev
Senegal Dr Mbayame Niang
Serbia Dr Vera Jerant-Patic
Serbia Dr Jasminka Nedeljkovic
Singapore Dr Ai Ee Ling
Slovakia Dr Hana Blaskovicova
Slovenia Dr Maja Socan
South Africa Dr Terry Besselaar
South Africa Dr Girish Kotwal
Spain Dr M. de Anta
Dr M. Pilar Perez-Brena
Dr Raúl de Lejarazu
Sweden Dr Annika Linde
Switzerland Dr W. Wunderli, Dr L. Kaiser
Thailand Dr Mrs.Pranee Thawatsupha
Taiwan Dr H-S Wu
Trinidad and
Tobago
Dr H. Vaughan
Tunisia Dr Amine Slim
Turkey Dr Neziha Yilmaz
United Kingdom Dr Maria Zambon
Dr B. Carman
Dr Pamela Molyneaux
Uruguay Dr J. Russi
United States Dr John Janda
Dr H. F. Maassab
Dr L. Grady
Venezuela Dr Jesus Querales
Viet Nam Dr Le Qyunh Mai
Dr Nguyen Tran Hien

22. WHO Global Influenza Programme: Vaccine Recommendations
GLOBAL
HEALTH
SECURITY
text
Fujian-California cluster transition

123. Introduction
Antigenic evolution
Evolution predictable?
Immune pressure to evolve
Pre-emptive vaccine updates

124. Cross-species transmission

125. Human and swine A(H3)
de Jong et al, J. Virol 2007.
HK68
FU02
Eurasian Swine

126. Human and swine
de Jong et al, J. Virol 2007.
HK68
FU02
Eurasian Swine

127. Human and swine
de Jong et al, J. Virol 2007. (phylogeny too)
HK68
FU02
Eurasian Swine

128. What next?

129. What next?
Bjorn Koel

130. RvB 230699 130
The genetic basis of antigenic change
Koel et al, Science, 2013

131. Site A
Site B
Site C
Site D
Site E
Wiley, Wilson, Skehel
Nature, 289, 373-378, 1981
Hemagglutinin structure

132. Site A
Site B
Site C
Site D
Site E
Wiley, Wilson, Skehel
Nature, 289, 373-378, 1981
Crucial
residue
Accessory
residue
RBS

133. 189
193 156 158
155
145
143
133
159
Crucial
residue
Accessory
residue
RBS

134. 189
193 156 158
155
145
143
133
159
Crucial
residue
Accessory
residue
RBS
Assay, RBCs, Wendy

135. What next?

136. What next, and when?

137. Introduction
Antigenic evolution
Evolution predictable?
Immune pressure to evolve
Pre-emptive vaccine updates

138. Fonville et al, Science, 2014
Judy Fonville
Sam Wilks

139. Fonville et al, Science, 2014

140. Fonville et al, Science, 2014

141. ●
MeantitrebenefitfromA/Sydney/5/97vs.A/Nanchang/933/95vaccination
−2−1012
● ●
A/Sydney/5/97A/Nanchang/933/95
HK68 EN72 VI75 TX77 BK79 SI87 BE92 WU95 SY97 FU02 WI05 PE09

142. ●
MeantitrebenefitfromA/Sydney/5/97vs.A/Nanchang/933/95vaccination
−2−1012
● ●
A/Sydney/5/97A/Nanchang/933/95
HK68 EN72 VI75 TX77 BK79 SI87 BE92 WU95 SY97 FU02 WI05 PE09

143. House 188, subject 1
10/11/1959
Female
House 145, subject 1
09/05/1960
Male
House 145, subject 2
10/06/1970
Female
●
MeantitrebenefitfromA/Sydney/5/97vs.A/Nanchang/933/95vaccination
−2−1012
● ●
A/Sydney/5/97A/Nanchang/933/95
HK68 EN72 VI75 TX77 BK79 SI87 BE92 WU95 SY97 FU02 WI05 PE09
Ha Nam household cohort study

145. Plus 69 others

146. Whenever response, backboost, ~400 individuals
Pre-Post Vaccination

147. 0
●
01234
A/Nanchang/933/95
●
MeantitrebenefitfromA/Sydney/5/97vs.A/N
−2−10
HK68 EN7
~100 Individuals. Solvay & CSL

148. 01234
A/Nanchang/933/95
●
MeantitrebenefitfromA/Sydney/5/9
−2−1
HK68 EN72 VI75 TX77
01234
A/Sydney/5/97
●
/97vs.A/Nanchang/933/95vaccination
012

149. Introduction
Antigenic evolution
Evolution predictable?
Immune pressure to evolve
Pre-emptive vaccine updates

152. Summary

153. Summary
The National Institute of Allergy and Infectious Diseases Cen
Research and Surveillance program has built a vital infrastru
influenza in animals, research on influenza pathogenesis, an
researchers and scientists. The multidisciplinary nature of th
respond to global pandemic events, make them a critical com
international efforts to control influenza. The ability to respo
warrant provides a significant advantage for public health ef
traditional NIH funding mechanisms. The Centers of Excellen
Surveillance (CEIRS) program fulfills an important niche for t

154. Terry Jones
Ana MosterinJudy Fonville Colin Russell
David Burke
Ron Fouchier
Nicola Lewis Ana Mosterin
Eugene Skepner
Bjorn Koel Sarah James Leah Katzelnick
WHO, FAO, OIE, CDC, MELB, NIID, NIRM, and NICs worldwide; VLA, HKU, St Jude
Ana Mosterin
Sam WilksTerry Jones
Barbara
Muehlemann Ramona Mogling Richard Smith
Erasmus
Jan de Jong
Walter Beyer
Guido van der Net
Guus Rimmelzwaan
Nic Masurel
Ab Osterhaus
Ron Fouchier
Australia
Malet Aban
Lumin Xue
Aeron Hurt
Ian Barr
Vietnam
Pham Quang Thai
Tran Nhu Duong
Annette Fox
Heiman Wertheim
Le Quynh Mai
Nguyen Tran Hien
Peter Horby
Ha Nam household cohort
WHO collaborating centers
and Essential Regulatory Laboratories
NICs worldwide
Solvay and CSL
Madison
Gabi Neuman
Eileen Maher
Yoshi Kawaoka