Fondation Mérieux, Les Pensières, Annecy. France
2009-03-30/2009-04-01
| Antigenic variation and immune evasion: understanding it and coping with it, implication for vaccine design.
Annecy, Les Pensières, March 30, April 1, 2009 |
BackgroundMulticellular organisms possess very sophisticated defense mechanisms that are designed to counter the continual microbial insult of the environment within the vertebrate host. The interaction between a pathogen and the mammalian immune system resulted in two basic transmission patterns. In the first one, pathogens replicate rapidly and are transmitted early, before the development of an effective immune response. The second transmission pattern is typified by persistent infection until there is an opportunity for transmission, which might not occur until long after a fully mature and effective immune response has developed. Evasion of host immune defenses may be achieved by antigenic variation, which is common in vector-borne and mucosally-transmitted pathogens. Although strain-to-strain variation in antigenic molecules (antigen diversity) is common, antigenic variation refers to a single strain specifically changing a subset of its antigens either to sustain ongoing infection or re-infect hosts even though the first infection was successfully cleared. Antigenic variation concerns proteins or glycoproteins (i) expressed at the surface of extracellular pathogens or at the surface of cells infected by intracellular ones, (ii) involved in adhesion or invasion to host cells or in cytoadhesion of infected cells, and (iii) often immunodominant.In parasites and bacteria, antigenic variation sensu stricto often involves specific multigene families devoted to that function and generally occurs at rates orders of magnitude faster than gradual accumulation of genetic alterations associated with random, non targeted mutational events. The genetic information for producing a family of antigenic variants is available in the cell but only one variant is expressed at a given time. Switching between members of a multigene family involves a complicated mechanism of activation and silencing.The mechanisms underlying antigenic variation are either based on transcriptional and epigenetic control (in situ switching), like in Plasmodium falciparum or Giardia lamblia, or on gene conversion (unidirectional recombination), described in parasites (Trypanosoma brucei, Babesia bovis) and bacteria (Borrelia hermsii, Neisseria gonorrhoeae, and Anaplasma marginale). A major conceptual issue is how sequential dominance of antigenic variants is achieved by a population of parasites within a host, each independently expressing a variant. Several theories have been developed, mainly from studies of Trypanosoma, Plasmodium and Borrelia.Exceptions to these rules have been recently demonstrated: organisms with diverse antigenic variants may co-exist within the same host (Treponema pallidum, M. genitalium) and the mechanism for antigenic variation may be reciprocal recombination, as opposed to gene conversion (M. genitalium).Antigenic variation also occurs in viruses, facilitating, in addition to immune escape or immune subversion mechanisms, persistent infections. Variation is not based on switching between members of multigene families, but rather on spontaneous mutations during viral replication. Examples are lentiviruses (HIV, FIV), HCV (hepatitis C virus), caliciviruses. Infection with one isolate also leads to multiple antigenic variants within one host.For some of the pathogens cited, which represent dramatic disease burdens within human or animal populations, numerous vaccine approaches have been tested with limited success. The immunodominant character and the roles in pathogenesis of the variant antigens represent difficult challenges. In the face of the highly efficient antigenic variation strategy of the immunodominant unique surface protein VSG, vaccines for protection against Trypanosoma brucei are not contemplated. Some 20 candidates are currently in development at different phases for malaria prophylaxis. Moreover, virulence evolution in response to vaccination needs to be considered during vaccine development. Genome sequencing of bacterial and parasite pathogens opens however new perspectives for prophylactic approaches. Immune evasion mechanisms other than antigenic variation (based on host immune system regulation or subversion) will not be discussed in this meeting (they were the main topic of previous meetings). The Conference’s strategic objectives include:1- To review the mechanisms and regulation of antigenic variation mammalian pathogens2- To review the types of ongoing vaccines approaches 3- To foster dialogue among different actors of the scientific and decisional communities involved in antigenic variation and vaccines development .Each speaker has been asked to specifically address one or more of these objectives in their presentation. There will be a professionally prepared report of the Conference's presentations and discussions including specific responses to the above objectives MONDAY, March 30, 2009 | 17h30-18h30 | „Registration | | | 18h30-18h45 | Welcome Address | C. LONGUET | | 18h45-19h15 | Keynote lecture: (Defining antigenic variation as opposed to phase variation and variability)
| | | 19h45 | „Welcome Dinner | |
TUESDAY, March 30, 2009| SESSION I | Parasites and bacteria: Antigenic Variation through transcriptional control „Chaired by: | | 08h30-08h50 | Epigenetic regulation of antigenic variation in Plasmodium falciparum | J.J. LOPEZ RUBIO | | 08h50-09h10 | Discussion | | | 09h10-09h30 | Constrains of antigenic variation on the development of vaccines against Malaria | A. CRAIG | | 09h30-09h50 | Discussion | | | 09h50-10h30 | „Coffee Break | | | | | | | 10h30-11h00 | Giardia lamblia mechnisms and vaccines | TE NASH | | 11h00-11h15 | Discussion | | | 11h15-11h45 | Ehrlichia canis, E. chaffeensis, their p28 paralogs, and mechanisms of persistence | D.H. WALKER | | 11h45-12h00 | Discussion | | | 12h00-14h00 | „Lunch | |
| SESSION II | Parasites and bacteria: Antigenic variation through gene conversion„Chaired by: | | | | | | 14h00-14h20 | African trypanosomes: can Variant Surface Glycoprotein gene conversion be considered a target for disease intervention? | R. McCULLOCH | | 14h20-14h40 | Discussion | | | 14h40-15h00 | Gene conversion in Babesia bovis antigenic variation and its implications for vaccine development | D.R. ALLRED | | 15h00-15h20 | Discussion | | | 15h20-15h50 | „Coffee Break | | | 15h50-16h10 | Gene conversion in bacteria: the Borrelia models | AG BARBOUR | | 16h10-16h30 | Discussion | | | 16h30-16h50 | Implication of antigenic variation for vaccine development: the Anaplasma marginale model | K.BRAYTON | | 16h50-17h10 | Discussion | | | 19h00 | „Dinner | |
WEDNESDAY, April 1, 2009 | SESSION III | Antigenic variation in viruses„Chaired by: Jacques LOUIS |
| 08h30-08h50 | Consequences of antigenic variation in terms of treatment in HIV | M. WAINBERG | | 08h50-09h10 | Discussion | | | 09h10-09h30 | Consequences of antigenic variation in terms of vaccines | B. AUTRAN | | 09h30-09h50 | Discussion | | | 09h50-10h20 | „Coffee Break | | | 10h20-10h40 | The antigenic variation in hepatitis C virus: consequences in vaccine design | A. FOURNILLIER | | 10h40-11h00 | Discussion | | | 11h00-11h20 | Molecular basis on antigenic variation in HIV | B. KORBER | | 11h20-11h40 | Discussion | | | 12h00-14h00 | „Lunch | | | 14h00-14h20 | Feline Caliciviruses | H. POULET | | 14h20-14h35 | Discussion | | | SESSION IV | Microbial evolution in response to vaccination„Chaired by: | | | 14h35-14h55 | |
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Organized by:
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Catherine Dutel / Seminar and Training Manager |
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Invited Speakers:
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J.J. LOPEZ RUBIO, A. CRAIG, TE NASH, D.H. WALKER, R. McCULLOCH, D.R. ALLRED, AG BARBOUR,M. WAINBERG, B. AUTRAN, A. FOURNILLIER, B. KORBER ,H. POULET, V.V. GANUSOV, MJ MACKINNON, K.BRAYTON.
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Deadline for Abstracts:
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2009/03/01
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Registration:
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Antigenic Variation and Immune Evasion March 30 - April 1, 2009 at Les Pensières Conference Center • Veyrier-Du-Lac • France • www.fondation-merieux.org Please complete and return to Ms. Amal Darghouth, before March 15, 2009. amal.darghouth@fondation-merieux.org - fax 33 (0)4 50 60 07 21 - phone 33(4) 50 64 80 80 NAME Family name......................................................................... First Name........................................................................... & ADDRESS INFORMATION Address............................................................................................................................................................................. Code/City......................................... Country........................................ Institute/Company.............................................. Phone.......................................... Fax...................................... Email............................................................................... HOTEL > Indicate which nights you will be staying: March 30 March 31 April 1 REQUEST > Indicate your room request : For one person For two people No room required Fondation Mérieux has rooms available within Les Pensières conference centre ; to receive assistance in the reservation process: amal.darghouth@fondation-merieux.org - phone 33 (0)4 50 64 30 52 REGISTRATION > Registration fees do not include hotel and travel fees. FEES Registration fees will be processed as a 200 € tax deductible donation per participant*. This fee includes: • participation in all conference sessions and workshops • gourmet meals throughout the conference Your donation will help to support Fondation Mérieux’s non profit activities and will allow us to continue to offer as many conferences as possible. Fondation Mérieux contributes through direct funding to approximately 80% of the total conference costs. We invite you to help us to continue to offer as many conferences as possible by making an additional contribution directly to Fondation Mérieux. We thank you for your participation and your contribution towards fulfilling Fondation Mérieux’s missions. * In certain cases post doctorate students may be eligible to attend the conference free of charge. > Registration fees (registration and additional contribution): 200 + ...................... = ...................... Euros PARTICIPANT REGISTRATION FORM PAYMENT > Indicate which means of payment you are using. DETAIL IMPORTANT: All payments should be made in Euros to Fondation Mérieux at least one week before the conference. Indicate the name the symposium and your name on all bank transfers, to ensure efficient handling. Banker’s draft Bank transfer : account n° 0000060690Q • Crédit Lyonnais - 18 rue de la République - 69002 Lyon - FranceSWIFT/BIC code CRLYFRPP • IBAN code FR49 3000 2019 5800 0006 0690 Q25 • VAT n° FR 723087 188 16 Visa Eurocard/Mastercard American Express Credit card number: ............................................................ Expiring date: ............................................................ Card holder’s name: ........................................................... I hereby authorize Fondation Mérieux to debit this credit card account for the total amount due. Having signed below I herewith confirm that I have read and I am fully aware of all registration/reservation and cancellations conditions. Date and signature: SPECIAL > Fondation Mérieux will provide all meals. Do you have special dietary requirements? REQUIREMENTS No pork Vegetarian Additional comments: ...........................................................................
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E-mail:
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catherine.dutel@fondation-merieux.org
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