Could a combination of OPV & IPV accelerate wild type poliovirus eradication? Nicholas Grassly

Transcription

1 Could a combination of OPV & IPV accelerate wild type poliovirus eradication? Nicholas Grassly

2 SAGE working group on IPV (est. Aug 2008) SAGE Members Elizabeth Miller, Chair Hyam Bashour Peter Figueroa Experts Nick Grassly, Imperial College London, UK Jacob John, Christian Medical College, India Antoine Kabore, HIV/AIDS, Tuberculosis and Malaria Division, WHO/AFRO, Burkina Faso Francis Nkrumah, University of Ghana Medical School, Ghana Walter Orenstein, Emory Vaccine Center, USA Kimberley Thompson, Kids Risk Project, Harvard School of Public Health, USA Walter Dowdle, Task Force, USA

3 Summary of presentation 1. Immunogenicity, clinical efficacy, mucosal immunity and herd protection offered by (e)ipv 2. Potential role of IPV in the accelerated eradication of wild type polioviruses 3. Potential role of IPV in the newly envisaged eradication endgame 4. Questions for SAGE

4 Immunogenicity of IPV on EPI schedule (6,10,14 weeks) Serotype Average % of children with serum IgG > 1:4 or 1:8 Range reported in studies weighted average from 11 studies summarised in Plotkin & Vidor 2007

5 Immunogenicity of IPV on EPI schedule Seroconversion * after 3 doses of intramuscular IPV given according to EPI (6,10,14 weeks) or US (8,16,24 weeks) schedule in Puerto Rico *defined as a >= 4 fold increase in neutralizing antibody titre over projected level based on decline in maternal antibodies; Dayan et al 2007 JID

6 Individual protection: clinical efficacy of IPV Location Schedule Efficacy % (95% CI) Reference Senegal IPV 89 (62 97) Robertson 1 et al 1988 Canada IPV 96 Varughese et al vaccination cards missing in one third

7 Mucosal immunity: systematic review of the prevalence of poliovirus shedding in stool after OPV challenge IPV compared with no prior vaccination

8 Mucosal immunity: systematic review of the prevalence of poliovirus shedding in stool after OPV challenge OPV compared with no prior vaccination

9 Mucosal immunity: systematic review of the quantity of poliovirus shedding in stool after OPV challenge In 4 studies that examined the quantity of poliovirus shed in stool samples, a 63 91% (or an absolute log 10 ) reduction was found among children vaccinated with IPV compared with unvaccinated children Three of these studies also examined the duration of shedding and two found a shorter period of shedding in IPV vaccinated children

10 Mucosal immunity: systematic review of poliovirus shedding in the nasopharynx after OPV challenge Only 4 studies that met inclusion criteria for systematic review Vaccine poliovirus only rarely isolated from nasopharynx irrespective of vaccination status 3 studies of shedding among contacts of children with poliomyelitis in the USA during found children vaccinated with IPV were less likely to have wild type poliovirus isolated from the nasopharynx In these same studies there was no significant association of IPV vaccination status with shedding in stool

11 Mucosal immunity: mechanism Transudation of IgG will contribute to virus neutralization Serotype 3 poliovirus specific secretory IgA after an IPV booster in individuals previously vaccinated with OPV ( ) or IPV ( ) IPV appears not to induce secreted IgA in the intestine unless there has been exposure to live poliovirus (mucosal priming) (Herremans et al. 1999) Cellular immunity to poliovirus not understood p/n ratio is the ratio of positive reaction in ELISA readings in the presence of Ag divided by the ELISA readings in the absence of Ag; Herremans et al 1999 J Immunol

12 Herd immunity from IPV experience in the USA Stickle et al 1964 cited in Plotkin and Vidor 2007

13 Herd immunity experience from other countries Sweden, Finland, Netherlands & Iceland achieved polio eradication with IPV only Other countries have switched to IPV and continue to be polio free (France, UK, USA) Outbreaks of poliomyelitis have been restricted to unvaccinated children although wild type poliovirus has been isolated from vaccinated children (e.g. Netherlands 1978, Schaapet al 1984,Oostvogel et al 1994; Finland 1984 Hovi et al 1986) OPV therefore often used to control these outbreaks Very little experience of IPV in low income countries

14 Impact of IPV on incidence of poliomyelitis in adjoining communities Vellore, India DPT DPT IPV Number of children Child yrs Children with poliomyelitis 17 0 Incidence /1000 child yrs John 1993 Rev Med Virol

15 Herd immunity experience in India Children number Prevalence % (n stools) Control (69/4527) study (49/8159) John 1993 Rev Med Virol

16 2. Potential role of IPV in the accelerated eradication of wild type polioviruses WHO position on pre eradication use of IPV during routine immunization covered by Polio vaccines and polio immunization in the pre eradication era: WHO position paper 2010 Wkly Epi Rec 85: Could IPV be added to vaccination campaigns to accelerate wild type poliovirus eradication?

17 Oral poliovirus vaccine (OPV) immunogenicity in lower income countries TJ John 1972,1976 Vellore, India

18 Clinical efficacy of oral poliovirus vaccine in Pakistan and Afghanistan: case control estimates Unpublished results deleted from the online version O Reilly ms in prep

19 Prevalence of serum neutralizing antibodies after a supplemental dose of IPV or trivalent OPV Country Age Seroprevalence Seroprevalence N Baseline (3OPV) +IPV N Baseline (3OPV) +topv Cote 6 mo % 94%* % 85% d Ivoire 1 9 mo % 97%* % 85% Gambia % 88%* 58 81% 81% Oman 3 9 mo % 100% % 99% Seropositivity was defined as an antibody titer 8. * Significant versus +topv group. 1 Moriniere B J, Lancet 1993, 341: Hanlon P, Lancet 1987, 1(8536): Sutter RW, NEJM :

20 Mucosal immunity: systematic review of the prevalence of poliovirus shedding in stool after OPV challenge effect of adding IPV to an OPV schedule

21 Knowledge gaps What would be the herd effect of a vaccination campaign with IPV (and OPV) in endemic areas? What coverage could be achieved? What age groups should be targeted? Number of doses/frequency of campaign use?

22 Ongoing and potential studies Ongoing or planned OPV challenge studies to measure mucosal immunity after an additional dose of IPV children aged 6 11 months, 5 6 years and years given a booster of IPV or bivalent OPV (Moradabad, India recruitment began October 2011) Children aged 9 59 months last vaccinated > 6 months prior to a booster of IPV or serotype 1 monovalent OPV (Vellore, India recruitment Spring 2012) others Larger scale demonstration projects would allow impact on vaccination coverage to be addressed Pakistan, Impact on wild type poliovirus transmission will not be clear until IPV used on a very large scale

23 3. Potential role of IPV in the newly envisaged eradication endgame Switch from trivalent to bivalent OPV during routine immunization would leave children unprotected against serotype 2 poliomyelitis Serotype 2 vaccine derived polioviruses are common and can fully revert to wild type poliovirus transmissibility and neurovirulence (e.g. Nigeria, Jenkins et al N Engl J Med) Routine trivalent OPV will be used until transmission of currently circulating vaccine derived polioviruses is stopped (WHO position paper: IPV alone may be considered an alternative to OPV alone (or an IPV OPV sequential schedule) only in countries that have the lowest risk of both WPV importation and WPV transmission. ) After this is achieved IPV could provide protection to these children, potentially in reduced schedule and/or dose to reduce costs

24 Seroconversion after 3 vaccinations with (A) 1/5 dose intradermal IPV (bioject) and (B) full dose intramuscular IPV (needle) at 6, 10 and 14 weeks Resik et al 2010

25 Immunogenicity depends on antigen content Results are for serotype 1, Salk 1955 JAMA and Salk & Salk 1978 reproduced in Plotkin & Vidor 2007; individuals were seronegative before vaccination

26 Individual protection: clinical efficacy of IPV Location Schedule Efficacy % (95% CI) Reference Senegal IPV 36 (0 67) Robertson 1 et al 1988 Senegal IPV 89 (62 97) Robertson 1 et al 1988 Canada IPV 96 Varughese et al vaccination cards missing in one third

27 Knowledge gaps Optimal scheduling and dosing full dose/ complete schedule Affordability Immunogenicity reduced dose/ reduced schedule Clinical efficacy of immune memory induced by IPV priming Herd effect of IPV against any serotype 2 vaccine derived poliovirus outbreaks Coverage that can be achieved through routine immunization and role of vaccination campaigns

28 Ongoing and potential studies SAGE IPV working group will address post eradication use of IPV in next WHO position paper Development of affordable and immunogenic IPV through research on Adjuvants Reduced schedules Different routes of administration Sabin or other attenuated poliovirus seed strains Experience of countries currently switching to IPV (e.g. Mexico, Yogyakarta Indonesia, )

29 Question for SAGE SAGE's opinion as to what role IPV might play in the context of wild poliovirus eradication and which, if any, additional research studies or evaluation projects should be undertaken to guide strategy in this regard.