Vaccination Present Future 2015.pdf

8/17/2019 Vaccination Present Future 2015.pdf

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Immunisations: past and future

Class IC2Course Tropical Medicine

Code TM

Title Immunisation: past and future

Lecturer Prof. Samuel McConkey

Date 10th September 2015

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn


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Objectives

• To understand, through examples, the success

of vaccines

• The concept of vaccines

• History of vaccines

• Future of vaccine development – e.g. Ebola


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• The story of control of meningitis

– Haemophilus influenzae b

– Streptococcus pneumonia

–Neisseria meningitidis subtype C

• The story of neonatal tetanus

• How to prevent cancer

– Hepatitis B vaccine


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Number of cases of invasive Haemophilus

influenzae subtype b per year in Ireland

0

20

40

60

80

100

120

1 9 8 7

1 9 8 9

1 9 9 1

1 9 9 3

1 9 9 5

1 9 9 7

1 9 9 9

2 0 0 1

2 0 0 3

2 0 0 5

2 0 0 7

2 0 0 9

2 0 1 1

From Health Protection Surveillance Centre, Dublin Sept 2014

Hib vaccine introduced


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From Centre for Disease Control, Atlanta, Georgia 2014


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Figure. 1. Number of Meningococcal C events on CIDR by Year & Quarter, Q1-

1999 to Q2-2014

From Health Protection Surveillance Centre, Dublin Sept 2014

Men C Vaccine introduced


7/21Source, hpa. org.uk


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Credit to Worldmapper.org

Irish Medicines Exports 2002 from UNCTAD data On-line 2005


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UNCTAD 2012 report World exports Irish

Medicine including veterinary $332b $25.1b

Organo-inorganic compounds $ 87b $23.6b

Pharmaceuticals excluding meds $134b $ 9.5b

Med device and appliances $ 68b $ 3.6b

Pfizer RingaskiddyOrganic Synthesis Plant No 4


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Neonatal tetanus


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Source, Lancet, and Journal National Cancer Institute


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How vaccines were made historically•

Live attenuated –

vaccinia, BCG, polio (Sabin)• Killed – Rabies (Pasteur),

• Adjuvanted- alum,

•Sub-units- Hepatitis B surface protein

• Conjugated vaccines,

– Hib, covalently linked to tetanus toxoid, Men B omp

– pneumococcus CHO linked to CRM197 (diphtheria t) – Men C linked to tetanus


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Future

• DNA vaccines- work in mice

• Vectored in vaccinia

•

Prime-boost• Polyvalent- 6 in 1, 23 valent PneumoVax

• H1N1 influenza A vaccine – AS03 & narcolepsy

• Individualised APC primed against cancers


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Ebola vaccine

• How to make one.

• Candidates

•

Pre-clinical trials• Clinical trials

• Licensure

• Marketing and distribution

Source: kenyon.edu


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How to make a vaccine

• Whole-cell killed XXX

• Live attenuated XXX

•

Sub-unit – Conserved sequences : Glycoprotein

– Immunogenic

– Adjuvants – antibodies or T cells

• DNA plasmids

• Vectored- Chimpanzee adenovirus

Judith M. White & Kathryn L.

Schornberg

Nature Reviews Microbiology 10,

317-322 (May 2012)


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Correlates of protection

• Use studies of partial protection

– Antibodies correlation with survival

– Neutralising Ab, how much? to which antigen?

– Passive transfer experiments

• CD8+ cytotoxic T cells

• CD4+ helper T cells

• Combination of above


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Animal model

• Mice

• Guinea pig

•

Hamster• Non-human primates

» cynomolgus

» rhesus

» baboons» African green


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Subunits

• Glycoprotein

Plasmid DNA

• Works in Guinea pigs

Adenovirus 5Has gone to Phase I study


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Expert Opin Biol Ther. Hoenen et al. Jul 2012; 12(7): 859 –872.Published online May 5, 2012. doi: 10.1517/14712598.2012.685152

Structure of ebolavirus and of ebolavirus vaccines protective in NHPs

Shown are schematic representations of ebolavirus (center) and VLP, rAd5,rVSV and rHPIV3 vaccine particles, as well as of the recombinant virus

genomes for rAd5, rVSV and rHPIV3. Ebolavirus genes and proteins are

shown in color (blue: glycoprotein, yellow: matrix proteins, red: nucleocapsid

proteins), whereas genes and proteins of the vaccine vectors are shown in

gray. For the rAd5 genome deletions in the E1 and E3 regions are indicated.

http://dx.doi.org/10.1517%2F14712598.2012.685152http://dx.doi.org/10.1517%2F14712598.2012.685152


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Pre-clinical evaluation-

Tested in animals

• Stability – temperature, time

• Purity, toxins, contaminants, LPS,

•

Mice immunogenicity – Antibody levels

– Neutralising antibodies

– T cell responses

• Toxicity and path – in 2 species mice, rabbits

• Distribution

•

Efficacy in animal models, incl. primates


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Clinical trials

• Phase I- immunogenicity in human, tolerability

• Phase II- efficacy, likely no trials in humans

Deployment based on safety andimmunogenicity in humans and

efficacy in animal models

LicensingManufacturing and distribution

Documents

Vaccination Present Future 2015.pdf