Immunity and Vaccines Immune system Virus persistence Immunity / memory / vaccines Neutr. Ab: successful vaccines!

Prevent penetration IgA systemic neutr.-opson.IgM/G adoptive transferable IgG IgM 1-2d, regulated by Ag-dose and structure (no negative selection) Control-elim. intracell parasites also in solid organs regulate longterm IgG cause imunopathology (negative selection) T B Ab

IMMUNO- PATHOLOGY: V known V IMMUNOPROTECTION IMMUNOPATHOLOGY V V AUTOIMMUNITIY: V not known unrecognized endogenous VS.

glycoprotein: LCMV-GPglycoprotein:IND-G rLCMV/INDGrVSV/LCMV-GP reverse genetic glycoprotein exchange between LCMV and VSV LCMVVSV-IND glycoprotein: LCMV-GPglycoprotein:IND-G

Only VSVG expressing viruses induce a neutralizing antibody response

Why autoimmune disease in humans mostly via antibodies? Why>> ! Why all vaccines that function protect via neutr. antibodies? First infection kills host: no memory needed Host survives first infection: memory not necessary

persistent virus from mother

Poliomyelitis – age distribution in Massachusetts 1912 – 1952

Maintenance of protection 1. Agent persists: TB, leprosy, HIV, HCV, LCMV Herpes viruses crippled: measles 2. Repetitive inf.: polio, bact. toxins 3. Antibody-antigen complex depots in lymph nodes and spleens

Conclusions: Persistent infections: numbers / variability T cell control – immunopathology – "tolerance" nAb essential (affinity maturation?) or escape All successful vaccines: nAb not successful: should (also) maintain act.T (not achieved yet, TB!) Maternal antibodies attenuate acute infections physiological vaccinations (incl. malaria, eggs) Non-cytophatic infections transferred via placenta / at birth / after birth (LCMV, HCV, Herpes) Resistance via T cells: HIV, HTV, TB Lepr. slow "Emerging" infections

H. Hengartner A.Althage M.Bachmann Th.Kündig P.Klenerman A.Ciurea U.Karrer Th.Fehr L.Hunziker M.Recher A.Ochsenbein B.Ludewig M.Pericin A.Lamarre U.Kalinke HP.Roost C.Lopez M.Martinic Th.Rülicke