New vaccines mean new strategies: A theoretical exploration of the impact of HPV/HSV vaccines.

Geoff Garnett

Department of Infectious Disease Epidemiology,Imperial College, London.

Department of Infectious Disease Epidemiology, Imperial College

Standard Thinking: The Critical Vaccination Threshold, pc

Eradication

0

0.2

0.4

0.6

0.8

1

0 2 4 6 8 10 12 14 16 18 20Basic Reproductive Rate, R0

Persistence

Mea

sles

Ru

bella

Cri

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por

tion

, pc

Hib

Department of Infectious Disease Epidemiology, Imperial College

• Efficacy of STD vaccines likely less than childhood vaccines.• Delivery of vaccines against STDs controversial?• Platform for vaccine targeting and delivery.

0

0.4

0.8

0 0.2 0.4 0.6 0.8 1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8

Prevalence

Take

Degree

Impact of vaccination sub elimination - simple theoryMeaning of efficacy vital.

Degree – protected from a fraction of challenges

Take – fraction protected from all challenges

vRY

0

11

Efficacy v

vR

Y 0

11

Department of Infectious Disease Epidemiology, Imperial College

The impact of behavioural reversals on endemic

prevalence - 50% vaccine efficacyIncreased risk increases the basic reproductive number

0

0.2

0.4

0.6

0.8

1

0 100 200 300 400 500

Percentage increase in risk behaviour

Eq

uil

ibri

um

pre

vale

nce

Degree

Take

Department of Infectious Disease Epidemiology, Imperial College

Proportion of each cohort effectively vaccinated

Cohort vaccination - endemic HIV prevalence‘Take’ type efficacy reduces susceptibility:

0

0.1

0.2

0.3

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8

Pro

port

ion

of s

exua

lly

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ve a

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30 y

ears

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er in

trod

ucin

g va

ccin

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Department of Infectious Disease Epidemiology, Imperial College

Reducing the effective and basic reproductive rate

0

2

4

6

8

10

12

14

16

0 20 40 60 80 100

Percent

Reduced Transmissionprobability

Effectively vaccinated

En

dem

ic P

reva

len

ce (

%)

Department of Infectious Disease Epidemiology, Imperial College

Risks of release from competition of more pathogenic strains?

1) Requires cross immunity 2) Requires that cross immunity not generated by vaccine3) Requires that frequency dependent selection is limiting

incidence of infection

What is additional influence of vaccination interacting with screening?

What is the impact of competing hazards in success of an HPV vaccine?

Department of Infectious Disease Epidemiology, Imperial College

Inci

den

ce I

CC

per

100

,000

Age

All HR HPV All HR HPV; screening HR HPV w/o 16, 18 HR HPV w/o 16, 18; screening

20 40 60 800

.0001

.0002

.0003

.0004

Department of Infectious Disease Epidemiology, Imperial College

% r

edu

ctio

n in

CIS

% reduction in hazard of HPV infection0 50 100

0

50

100

Department of Infectious Disease Epidemiology, Imperial College

Conclusions

• STD vaccines with ‘limited’ efficacy could provide powerful intervention tools.

• Impact of an HSV vaccine depends upon impact of viral shedding.

• Targeting unlikely to be useful for vaccines against viral STDs.

• HPV vaccination strategy needs to include ongoing effective screening.

• Little risk of competitive release of virulent HPV types