The day started with a symposium on past experience from
typhoid vaccine implementation: translating global policy to country use. This
was moderated by Kim Mulholland, LSTM, UK. The talk started with Nepal Vi – ps
introduction in Nepal. Dr. Pradhan urged international community to assist GON
to introduce typhoid vaccine in its national EPI program. The second talk was
given by Leon Ochai on vaccine introduction in Pakistan. There was also mention
of DOMI program and its relation to assess vaccine effectiveness in the real
public health situation with >60 % effectiveness > 5 years of age. It was
introduced as school based vaccination. I could see that the coverage was
average around 60 %. It was related with trust to the system, the reason for
low coverage.
Where do we stand?
- Burden of TF – high along with MDR / age of infection as low as 6 months
- Vaccine use: TF vaccination is efficacious and feasible / capability for vaccinating school children
- National financial resources limited
- Global agency financing will facilitate the vax introduction and help in controlling this disease
- Sri Lankan experience: Jaffna (IDP camps) has the highest incidence of TF followed by Colombo (with highest population) in SL. Vaccine being given to outbreak situation / pilgrims / food handlers / close contact of patients / where water sanitation (poor)/health professional / armed forces / children with frequent of diarrhea. However, there is high literacy / improvement in WSH. There is also environmental surveillance.
- surveillance – sentinel + lab surveillance
- Antibiotic monitoring
- Immunization in High risk areas
Conclusion: Government is willing to vaccinate and GAVI is also
willing to finance this initiative. We should not hesitate to move forward.
Also, we need environmental sampling + improvement in WASH
Integration of TF vaccine in NI Schedule: opportunities and
challenges from industry (Bharat Biotech – India). There is higher disease
burden in urban so urgent need for its control. (Ochiai + Florian’s paper)
Typbar – tcv (6 months and above / single dose / IM – what r the key
consideration (WHO ECBS guideline on Typhoid vaccine use)
- Primary above 6 months / Single dose / at least 6 months of gap for boost / or school based booster
- Current guidance available NIH efficacy studies
- New Vaccine Introduction from WHO perspective (Principle, Practices and Realities) -
- Moving fast
o
Measles vaccination
o
HiB introduction
o
Rubella vaccination
· Slow to medium progress
o
JE vaccine – regional vaccine
o
Pneumococccal
o
Rota Vaccine
o
HPV vaccination – cervical cancer
Various scenarios
·
Scenario A - ??
·
Scenario B – low income countries – GAVI funded
/ sustainability?
·
Scenario C – Gray area / prioritization
Key point to consider – decision making process
·
Burden of disease – various factors (eg
incidence / mortality / DALY)
o
Accuracy of the burden studies (syndrome sx may
overestimate)
·
Factoring in vaccine efficacy and its
effectiveness – looks into overall effectiveness of the vaccine
o
Herd effect / impact
Key message
·
Vaccine effectiveness > efficacy
·
Vaccine factors – age / booster / dosing …..
·
Alternative ways to control also available but
for example measles – vaccination is the only option
·
Cost – opportunity cost / cost benefit
·
its priority in government
·
Return on investment
·
Health budget
·
Global agenda (political / global initiative)
Question and answer session
·
what is the vaccine efficacy among 2 to 5 years
of age
·
Some voice against using the word ‘alternative”
in relation to vaccination e.g. HPV vaccination
·
Typhoid vaccination – John Crump interested with
vaccination against frequent in acute diarrheal illness.
·
Breiman – 2 to 5 years of age vaccine efficacy (factors like fear / poor
acceptance might have influenced the low efficacy rate among 2 to 5 years)
·
The effect of taking consent may have an effect
on low coverage
·
Dr. Bhutta gave a clear and succinct explanation
of why low coverage in Pakistan.
Next symposium is on development of vaccines against
typhoid, paratyphoid and NTS. This is the key area where I have an interest.
This is moderated by Adwoa Bentsi Enchilli, WHO, Geneva, Switzerland
Ghananian proverb – lesson to be learnt from past
Typbar – TCV (Bharat Biotech, India)
·
Safety and immunogenicity in healthy infants,
children and adults in endemic areas
·
control – Typbar (Vi – PS)
·
dose = 0.5 ml / cold chain needed
·
anti Vi igG 6 wks post vaccination – 1 endpoint
·
Safety across 6 months – 45 years
·
Results:
o
safe in all age group
o
Immunogenic (high IgG response) also in < 2
years
o
Persistent in immune response and also memory
response
o
antibody avidity is important for qualitative
assessment
o
Open label / controlled trial - TypBar TCV / Typbar
§
Conclusion – safe / immunogenic / immune
response persistent < 2 years / booster needed
§
Measles interference study underway
o
My question – Bharat Biotech is way ahead with
their conjugate vaccine, how we are going to deal with it as we are working
with Vi – DT vaccine
Vi - DT vaccine development – Bio Farma
§
our desire to move from medium > high
priority in WHO list of vaccine
§
Target Product Profile (TPP)
§
Process development / GMP process – master seed and working seed
§
Process flow (Vi Polysachharide)
§
ELISA / NMR /HPAEC method
§
WHO TRS 987 – requirement
§
Vi DT conjugation Process
o
Carrier protein prep
o
Vi PS preparation
o
Conjugation
o
Diafiltration
§
HPLC profile
§
Nonclinical immunogenicity studies (who
guideline)
Vi CRM 197
o
CRN
o
Conjugation kinetics as a process map
o
Bulk conjugate vs. Formulated Bulk
o
Study plan – mice study
Live oral vaccine – M01ZH09 (from parent Ty21a with some
changes) Ref: Waddington et al, J Infect 2013
o
Vax efficacy / correlates of protection
o
Vaccine efficacy – study design
o
blinded arm (Placebo vs M01ZH09)
o
Open arm (Ty21a)
o
LPS as surrogate of efficacy
o
Then challenge with TF bacteria / diagnosis
after challenge (temperature or Blood C/S)
o
Dose escalation study
o
LPS vs. Flagellen vs. Vi
Bivalent Core and O PS (COPS) – flaggelin conjugate vaccine
against iNTS and typhimurim infections
o
key - phase 1 flaggellin subunit serves as the
carrier protein – target for immune response
Interesting discussion – I guess on emerging considerations
for iNTS disease prevention moderated by John Crump, University of Otago, New
Zealand
Typhoid conjugate vaccines for public use: overcoming
barriers moderated by Zulfiqar Bhutta, University of Toronto, Canada
TF vaccine for public health use: overcoming barriers:
moderated by Zulfiqar Bhhutta
o
Current WHO position of TF (2008) – recognition
as serious health problem/significant public health burden/local
epidemiology/high risk population must be the target/ there are also inadequate
data on conjugate vaccine (t cell response / ? young age group)
§
national epidemiological data – rapid assessment
tool to map the disease epidemiology (better describe the local epidemiology)
§
Lack of validated assay
o
GAVI – Vaccine Investment Strategy (VIS)
o
2008 HPV/JE / rubella, typhoid conjugate
o
2011 interest in typhoid conjugate
§
WHO PQ and recommendation
§
GAVI program window decision
§
Program implementation
§
Vaccine evaluation
·
vaccination scenarios
·
Demand forecast
·
Develop impact estimates
·
Develop cost estimates
·
Assess other disease / vaccine feature
o
International Vaccine Institute (IVI) - landscape of what IVI is doing in Vi DT vaccine
development
o
Gates Foundation - Stringent and focus / fulcrum
of knowledge, innovation and technology / accelerate the product development
program (PDP) / focus and ambitious / using the vaccine so we can eliminate it
(nationally / regionally)/ integrate vaccine and WSH or other strategies
necessary / engagement – innovation so we can address
o
GAVI process / SAGE – uncertainties re: disease
burden – magnitudes / distribution, target age group, strategy utilizing
o
micro planning of deployment – generate evidence
/ advocacy / once WHO pq we can use it also convince the investors / also
generate demand – in direct communication with policy makers so we convince
them, prepare ground for deployment of vaccine, guidance of regulatory authorities
at country level
o
GAVI – key is evidence / disease burden data –
matrix of investment
o
Immunization strategy need to be carved out and
political will is also important / political commitment is always need – local
champions and translating local data and connecting with policy groups through
advocacy and communication
o
Need for efficacy data
o
Lack for good diagnostics so this could help
surveillance
o
Transfer of plasmid is on threat??
o
Nepal could advocate strongly in WHA through
executive body – how can we move forward???? / Position should focus on
implementation part.
o
Global Typhoid Initiative – need
o
description, discovery, development, delivery
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