GRF 2nd One Health Summit 2013: Presentation by Jérôme Denis, IMAXIO SA

1. OVERVIEW ON HUMAN VACCINES
AGAINST LEPTOSPIROSIS
Jérôme DENIS, Ph.D.
Associate Director of development
18/11/2013
IMAXIO SA

2. VACCINES :
For who ? For what (in which
epidemiological context) ?
Which Efficacy/Safety ?

3. FOR WHO / FOR WHAT ?
CASE 1
Endemic disease / Strain involved
well identified
High public health priority
Development of human vaccines
by national institute
Mass vaccination in specific areas
(general population – child/adults)

4. FOR WHO / FOR WHAT ?
CASE 2
Disease on specific overexposed
workers / Strain involved well
identified
Workers health priority
Development of human vaccines by
national institute or private company
Vaccination on specific workers
populations (adults)
Target workers populations : farmers, sewer workers

5. GENERAL CONSIDERATIONS
 Same technical approach (« Old fashion » - no recombinant
technology) : inactivated bacteria
 Most of these vaccines :
were not developped as pharmaceutical products with a market
authorization dossier (Australie, Israel)
(exception : France, Japon)
Are not available anymore (Japan)
With an unknown status (Russia, China)
 None of them protect against all circulating strains but focused on
most important one

6. FOR WHO / FOR WHAT ?
CASE 1 / VaxSpiral ®, Cuba

Vaccine : 3 strains + adjuvant
Control
group
N
Number of
leptospirosis
cases

Vaccine
group
VACCINE
EFFICACY
App. 50 000
people
App. 50 000
people
56
12
78%
Global impact :
 1996—2001 : 1,7 millions vaccinated people in Cuba
 Incidence rate : divided by 5 from 1994 to 2001
(Martinez et al., 2004)
(Gonzales et al., 2004)

7. FOR WHO / FOR WHAT ?
CASE 1 / VaxSpiral ®, Cuba
%
Malaise
32
Headache
15-20 %
Fever
10 %
Erythema/Oedema/induration
3-5 %
Pain
10-15 %
SAFETY :
Difficult to conclude (statistics on 950 people only / quite high levels /
no long term datas) but no severe adverse effects reported during the
clinical trial
(Martinez et al., 2004)
(Gonzales et al., 2004)

8. FOR WHO / FOR WHAT ?
CASE 2 / SPIROLEPT ®, France
Launched in 1979 in France
1 ml/syringe
Inactivated bacteria Serovar Icterohaemorrhagiae strain
Verdun
Subcutaneus injection
Conservative : Thiomersal
No Adjuvant
Vaccination protocol :
D0 / D15/ Month 4-6 / Every 2 years
Target populations :
Exposed (adult) populations
(sewage/pisciculture/agriculture/building workers/fireman)

9. FOR WHO / FOR WHAT ?
CASE 2 / SPIROLEPT ®, France

No leptospirosis cases in a followed sewers population (between 600 et 800 people) :
from 1.3 case/year (1951-1979) to 0 case/year (1981-1988) (Baranton, 1990).

No leptospirosis cases in the vaccinated population reported to our
laboratory or the french regulatory agency (ANSM)

10. FOR WHO / FOR WHAT ?
CASE 2 / SPIROLEPT ®, France
Study
Number of
vaccinees
/vaccinations
Local reactions
Systemic
reactions
CONCLUSION (from the
authors)
Mailloux and al.
1982
N=454/1157
injections
7 (not described)
3 cases (nausea)
« good tolerance except local
reactions during the 4 th boost
»
Benbrick and al.
2001
N=50
Pouliquen et Catalina,
2000
N=7375 -12531
0.33-0.56%
0.25-0.42%
« its has a good safety profile
in routine use »
Laurichesse and al.,
2007
N=60 (SC/IM)
40-60% sc
13-20% im
0-4% sc
0-13% im
“The results of this prospective
clinical trial
confirm the good safety profile
of the anti-leptospiral
Vaccine »
3/50 skin erythema and induration
« good tolerance […] but
necessity to have datas after
the 1st boost »
CONSISTENT with our pharmacovigilance database

11. FOR WHO / FOR WHAT ?
CASE 2 / SPIROLEPT ®, France
SINCE 1979
More than 800 000 distributed doses
From 1 to 16 injections / person
Good efficacy profile in target populations
Good safety profile

12. CONCLUSION AND DISCUSSION
• HUMAN VACCINES AGAINST LEPTO HAS BEEN WIDELY USED
IN DIFFERENT COUNTRIES, DIFFERENT EPIDEMIOLOGICAL
CONTEXTS
• THEIR EFFICACY AND SAFETY PROFILE ARE GOOD
• THEIR CONTRIBUTION IN LEPTO PREVENTION IN TARGET
POPULATION WAS SCHOWN TO BE SIGNIFICATIVE
PROPOSITION FOR GLEAN (PREVENTION PILAR)
THE POSSIBLE CONTRIBUTION OF A VACCINE AS SPIROLEPT COULD
BE TO PROTECT PEOPLE :
OVEREXPOSED DURING OUTBREAKS (RESCUE PEOPLE, FIREMAN)
OVEREXPOSED BY THEIR JOB (SEWERS WORKERS) BASED ON THE
FRENCH EXPERIENCE

13. CONCLUSION AND DISCUSSION
Progress in disease
knowledge
Progress in lepto research
(microbiology, immunology)
Epidemiology/ diagnostic tools
Collaboration with veterinary
industry
« Universal »
vaccines
development
Public health authorities
support