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

BAb

IMMUNO-PATHOLOGY:

V known V

IMMUNOPROTECTION

IMMUNOPATHOLOGY

V

V

AUTOIMMUNITIY:

V not known unrecognized endogenous

VS.

glycoprotein: LCMV-GP glycoprotein:IND-G

rLCMV/INDG rVSV/LCMV-GP

reverse genetic glycoprotein exchange between LCMV and VSV

LCMV VSV-IND

glycoprotein: LCMV-GPglycoprotein:IND-G

Only VSVG expressing viruses induce a neutralizing antibody response

3 8 14 20

642

108

12

<1

time after infection (days)

642

108

12

<13 8 14 20

time after infection (days)

VSV-IND neutralization rLCMV/INDG neutralization

3 8 14 20time after infection (days)

642

108

12

<1

rVSV/LCMV-GP neutralization

3 8 14 20time after infection (days)

642

108

12

<1

LCMV-ARM neutralization

2x104 PFU rLCMV/INDG i.v.

2x104 PFU VSV-IND i.v.

2x104 PFU LCMV i.v.

2x104 PFU rVSV/LCMV-GP i.v.

2x107 PFU rVSV/LCMV-GP i.v.

total Ig IgG

LCMV HIS

WEN-3 mAb

Why autoimmune disease inhumans 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 virusfrom mother

Poliomyelitis – age distribution in Massachusetts 1912 – 1952

Years Percent0 – 4 years

Percent5 – 9 years

Percent10+ years

1912-1916 70 18 121930-1934 28 38 341948-1952 18 27 55

Modified from: Nathanson,N. Am J Epidemiol 1979; 110:672-692.

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: nAbnot successful: should (also) maintainact.T (not achieved yet, TB!)

• Maternal antibodies attenuate acute infectionsphysiological 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. AlthageM. Bachmann Th. KündigP. KlenermanA. CiureaU. KarrerTh. FehrL. HunzikerM. Recher

A. Ochsenbein B. LudewigM. PericinA. LamarreU. KalinkeHP. RoostC. LopezM. MartinicTh. Rülicke