Vaccines against Covid-19: A Gamechanger in a global pandemic

tjacobs@bnitm.de Protozoa Immunology

The problem in numbers

Major risk factors for severe disease:

Age
Gender
Adipositas
Diseases
Genetic factors (?)
Pre-existing immunity to common cold CV (?)
Aging of the immune system and severe disease
 How can the immune system defend us?

• The Spike protein is binding to the ACE2 protein expressed on many

human cells.
• Neutralizing antibodies prevent infection.
 How long are we protected after recovery?

Experimental infection with common cold corona virus

Not surprising since we all know that we can get more often a common cold in our life!

Callow et al., 1990

 What about mutations?
To date 12.000 mutations are found but only some are making the virus fitter!

Only one amino acid exchange leads an increased virus production (increased infectivity!)

Q: Does this leads to a more severe disease?

Q: Does this lead to an decreased protection by natural aquirred or vaccine-induced antibodies?
 Cytotoxic T cells can kill virus-infected cells
A redundant immune arm providing protection in addition to antibodies

T cells recognize a large variety of virus fragments and their function is

much more resistant to viral mutations.
 May this happen again?

Human coronavirus OC43 and the ‘Russian flu’ pandemic

A pandemic of respiratory disease known as the ‘Russian flu’ occurred

in 1889 and 1890 and caused approximately one million deaths. This
pandemic has been speculated to be an influenza. A study from 2005
showed that OC43, which is a human coronavirus, may have
caused ‘Russian flu’. This makes it plausible that OC43 — which is still
circulating in humans, causing common colds — was the causative
agent of this pandemic.

This suggests SARS-CoV-2 is not the first coronavirus to cause a

pandemic and, given the frequency of outbreaks (SARS-CoV in 2003
and MERS CoV since 2012), it is likely not the last one.
COVID-19 TIMELINE
and development for second-generation malaria vaccines or vaccines against other neglected tropical
diseases.
In contrast: Vaccine-Development in
Malaria
44 vaccine candidates with 6 different principles
 Different methods to deliver cargo to dendritic cells
mRNA coding for the SPIKE protein is
packed in small lipid vesicles. These can be
uptaken by cells and the mRRNA is
translated into protein beeing
immunogenic.

Pro:
Immune response is focussed against SPIKE
mRNA can be easily edited
Not highly immunogenic

Cons:
Novel technology (special manufacturing)
Expensive

A non-replicating virus infect cells,

which produce SPIKE protein from
viral mRNA. The protein is
immunogenic.

Pro:
Easy to manufacture
Highly immunogenic

Cons:
To immunogenic
Immunity is induced against the
vector AND the spike protein
 The different phases in vaccine development

• Phase I: Safety profile on very few probands

• Phase II: Dosage and Efficacy

• Phase III: Up to 15.000 thousand participants either getting

the vaccine or control.
 Outcome of the Astra Zeneca Phase 3 Trial

Looks great but numbers are small

Voisey et al., The Lancet

But even in Phase 3 numbers are small
 Israel: Signals of Hope!
Israel made a contract with Pfizer and started a
massive vaccine-campagne. Vaccination was sceduled
according priority and age.

1. >60 j

2. >50 j

3. >40 j

4. >35 j
Due to this massive amount of data we can judge vaccine
efficacy in “real life“.
Can we stop the pandemic by vaccination?
Strong reduction of hospitalizations (severe disease)
 Major obstacles

• Amount of vaccines doses and coasts

• High vaccination rates are need for herd immunity

• Possible adjustments for vaccines due to mutations

• Seasonal boosting?
 What do we know?

• Licensed vaccine show mild side effects but vector

based vaccine may induce very rare severe side
effects
• High efficient protection against severe disease
• High efficacy protection against infection
• Even the first shot provide already high protection
rates
 What we still need to know?

• How long the protection will last?

– Against Infection / Infectivity
– Against Hospitalization / Severe disease

• When mutations will occur that reduce protection?

• What about (very rare) side effects?

Thanks !

Questions?