# Presentation: 045158

## PNEUMOCOCCAL CONJUGATE VACCINES FOR ADULTS

**Peter R. Paradiso, Ph.D.**
**Wyeth Vaccines**

**ISSUES AND CHALLENGES**

## Pneumococcal Conjugate for Adults Issues & Challenges

**CONJUGATE VACCINES WILL HAVE LESS SEROTYPE COVERAGRE THAN PS (23 valent)**
- Measuring the benefit of improved efficacy vs. coverage
- How will conjugates be used in the context of PS
**CAN EFFICACY TRIALS BE DONE?****	**
- Invasive disease vs. CAP
- With or without PS
**CAN CONJUGATES BE LICENSED ON THE BASIS OF IMMUNOGENICITY?**
- What measures?

## Issues with the PS Vaccine

**Duration of Immunity**
- What age to give the first dose?
**When / if to give subsequent doses**
- How to monitor
**Hypo-responsiveness**

## Pneumococcal Conjugate:  Product Profile

**Efficacy**
- Invasive disease
- CAP
**Can give repeated / periodic immunizations **
**        ****(any time relative to last conjugate or PS)**
- No hypo-responsiveness

## Immunogenicity Issues

**What are the best measures?**
- ELISA / OPA / % Responders
**What does “priming” mean in an adult?**
- Boost vs. reimmunizing
- Do conjugate vaccines prime or boost?
**Are certain serotypes in the PS less efficacions?**
- Are those the target for conjugate?

## Estimated IPD efficacy of 23-valent PncPS  vaccine

**Estimated IPD efficacy of 23-valent PncPS  vaccine**

- Butler et al JAMA 1993

- Estimated Efficacy (%) plus 95% C.I.)

## Most Common Serotypes causing Invasive Disease in > 65 y olds, USA, 1998 (n=1031)

**Most Common Serotypes causing Invasive Disease in > 65 y olds, USA, 1998 (n=1031)**

- Robinson et al 2001 JAMA

- % of IPD

- % coverage

- NR

## Relative Efficacy of Most Common Serotypes causing Invasive Disease in > 65 y olds in the U.S.

- Robinson et al 2001 JAMA

- % of IPD

- NR

- 60-80% efficacy

- 40-60% efficacy

- no significant efficacy

- contained in the 23-valent PncPS vaccines

- % coverage

## Immunogenicity of PS Vaccine Most Common Serotypes causing Invasive Disease in > 65 y olds in the U.S.

- Robinson et al 2001 JAMA

- % of IPD

- NR

- 60-80% efficacy

- 40-60% efficacy

- no significant efficacy

- contained in the 23-valent PncPS vaccines

- % coverage

## Immunogenicity of Conjugate Vaccines in non-infant populations

**Absolute Response to Conjugate**
- In naïve and previous PS vaccinees
**Response to conjugate or polysaccharide booster**
**ELISA vs. OPA vs. % responders**
**Serotype specificity**

## Hodgkin’s Patients/7-OMPC/mean age 39, n=38/group Chan et al JID 1996

- IgG (ug/ml)

## Immunogenicity of an 11V conjugate in healthy adults				Wuorimaa et al. (2001) 

- IgG (ug/ml)

## PncCRM OS 5-V Priming for PS Booster Response in 50-85 year old adults

*Powers et al JID 1996*

- 6 Month Interval
*N=23/group*

## 4

- 6B

- 14

- 18C

- 19F

- 9V

- 23F

- Immunogenicity (OPA) of PncPS-CRM 7-V or
- PS in Sickle Cell Children & Adults (n=12/group)

- Vernacchio et al JID 2000

**8 Weeks Interval; mean age 13 yrs**

## 4

- 6B

- 14

- 18C

- 19F

- 9V

- 23F

- PncPS-CRM 7-V Priming for PncPS Booster Response (OPA) in Sickle Cell Children & Adults (n=12/group)

- Vernacchio et al JID 2000

**8 Weeks Interval; mean age 13 yrs; **
**no boost by ELISA**

## Ability of Specific Serotypes to Elicit an ELISA response 

- Ability of Specific Serotypes to Elicit an ELISA response
- in PncPS non-Responder Populations

- Children 2-13 yr olds; n=17; PnuImune

- # of children with >1.3 mg/ml or 4-fold rise

*Sorensen PIDJ 1998*

## Ability of Conjugates to Elicit an ELISA response in PS non-Responder Populations

**# of children with >1.3 mg/ml or 4-fold rise**

- Children 2-13 yr olds; n=17; *PncCRM7; Pnu-Imune*

**Ability of Conjugates to Elicit an ELISA ****response in PS non-Responder Populations**

*Sorensen PIDJ 1998*

## Conclusions

**Data derived from very small data sets and may be serotype dependent **
**Conjugate can induce a response in adults even if  previously primed with PS vaccine**
**Conjugate can “prime” for a boost with either another conjugate dose or a PS vaccination**
**Suggestion that poorly immunogenic PS serotypes may respond to conjugate**
**There is little data in the elderly target population**
- Is there relevance to data in healthy adults?