East Coast fever – outlook for a new vaccine

Vish Nene

Workshop on the distribution, delivery and improvement of the

Infection and Treatment Method vaccine for East Coast fever

Nairobi, 19-20 August 2014

A live vaccine via ITM for the control of ECF

A live infection and treatment based method of vaccination

Caused by Theileria parva – a tick transmitted pathogen

Vaccination method developed by KARI and ILRI in mid-1970’s

The Muguga cocktail a commercial enterprise at CTTBD

Entry points for subunit vaccine intervention

Infected R. appendiculatus ticks

schizont-infected cells

sporozoites

piroplasms

merogony

Antigenic diversity - a hallmark of T. parva

sporozoite neutralizing Abs

sporozoite

bovine cell

schizont-specific CD8 killer T-cells (CTLs)

CTL

P

CTL

P

Technical advances in DNA/RNA/protein sequencing, glycomics,

molecular & cellular biology, immunology, bioinformatics, nano-tech,

computational biology, structural biology, microbiomes, etc.

New paradigms in science are accelerating vaccine development research

1. Identification of candidate vaccine antigens

2. Immunogenicity studies with antigens

3. Laboratory challenge studies

4. Contained field trials

p67N

p67M

p67C

21 225

226 571

572 651

9 709

Average

sporozoite

bovine cell

Parasite neutralizing Abs

Antibodies to p67 mediate immunity to ECF

A novel human antibody discovery platform

T-cell antigen discovery pipeline at ILRI - I

ACTGGTACGTAGGGCATCGA

TCGACATGATAGAGCATATA

GCATGACGATGCGATCGACA

GTCGACAGCTGACAGCTGAG

GGTGACACCAGCTGCCAGCT

GGACCACCATTAGGACAGAT

GACCACACACAAATAGACGA

TTAGGACCAGATGAGCCACA

TTTTAGGAGGACACACACCA

Bioinformatics

tools

Predict ~ 5000

gene sequences

& list candidate

vaccine antigens

Clone genes of

vaccine interest

Filter genes via IFN-g ELISPOT

and lytic assays

T. parva genome sequence

A

Random cDNA

library

B

Candidate CTL antigens

Map CTL epitopes

T-cell antigen discovery pipeline at ILRI - II

By Anne Mølgaard

High information positions

HLA-A0201

Pep deinMHCgroove Pep desexhibitamo f

Variousalgorithmsavailableforpredic onofpep deepitopes

[Peptide]

Control BoLA-N*04101/

no peptide BoLA-N*04101/Tp227-37 BoLA-N*04101/Tp229-37

CD

8+

(P

erC

P)

Flow cytometry assay

Mapped parasite CTL antigens/epitopes

CTL epitope Peptide sequence MHC class I

gene

BoLA sero-type

Tp1214-224 VGYPKVKEEML N*01301 A18 (HD6)

Tp227-37 SHEELKKLGML T2b~

Tp249-59 KSSHGMGKVGK N*01201 A10 (T2a)

Tp296-104 FAQSLVCVL T2c~

Tp298-106 QSLVCVLMK N*01201 A10 (T2a)

Tp4328-336 TGASIQTTL N*00101 A10 (5.1)

Tp587-95 SKADVIAKY T5~

Tp7206-214 EFISFPISL T7~

Tp8379-387 CGAELNHFL N*00101 A10 (5.1)

East Coast fever vaccine trials in cattle

One candidate B-cell vaccine antigen

~50% cattle immune to challenge in lab trials

How can this be improved?

Twelve candidate T-cell vaccine antigens

~30% cattle immune to challenge in lab trials

How can this be improved?

An East Coast fever R & D consortium

Inception workshop: 27-29th Jan 2014

Antibodies

Killer T-cells (CTLs)

Map new pathogen antigens

Map host response to infection & vaccination

Comparative pathogen genomics

Fill knowledge gaps for vaccine development & proof-of-concept (POC)

Compare different vaccination systems

Improve live vaccine – sporozoite counts

1. Enumerate live sporozoites 2. Relate sporozoite counts to infectivity 3. Relate sporozoite counts to immunogenicity

Guava easyCyte™ 5 high power laser (Merck-Millipore)

Vaccines?

Novel acaricides?

Anti-tick?

A role for vector control?

ECF Consortium -POC – in four years

1. Best bet sporozoite antigens 2. Best bet schizont antigens 3. Best bet delivery systems 4. Combination of sporozoite and schizont antigens

Phase 1: 70~80% immunity to defined parasite challenge/defined cattle

Phase 2: broad-spectrum immunity

The presentation has a Creative Commons licence. You are free to re-use or distribute this work, provided credit is given to ILRI.

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