# Presentation: 383704

## A model to compare potential benefits of new pneumococcal vaccines with the current 23-valent polysaccharide pneumococcal vaccine in the elderly

- Alicia Fry1, Elizabeth Zell1, Anne Schuchat1, Jay Butler2, Cynthia Whitney1

- Respiratory Diseases Branch1,DBMD and
- Arctic Investigations Program2, NCID, CDC

## Pneumococcal Disease and Vaccines in Older Adults

- 23-valent polysaccharide vaccine (PPV-23) is recommended for use in all persons 65 years
- Despite this, nearly 20,000 cases of invasive pneumococcal disease (IPD) occur in elderly each year
- Most deaths due to IPD occur in the elderly

## Model objectives

**Part 1**: Estimate the effect of the current 23V-pneumococcal polysaccharide vaccine on pneumococcal disease in the elderly
**Part 2**: Compare the potential effectiveness of 23V-PPV to new vaccines at preventing:
- invasive pneumococcal disease (IPD)
- pneumococcal pneumonia

**Notes:**
Currently, polyvalent polysaccharide vaccines are licenced for use in adults.  

These vaccines contain capsular polysaccharide from 23 of the more than 90 pneumococcal serotypes.  

The 23-valent vaccine was licensed for use in 1983, and replaced a 14-valent vaccine licensed in 1978.  

The 23 serotypes in the PPV cause more than 85% of IP infections in person 65 or older.

## Factors that influence a vaccine’s effect on disease 

- Disease Prevention

- Proportion of target
- population vaccinated

- Number of serotypes
- covered by vaccine

- Duration of protection

- Vaccine
- Effectiveness (VE)

## Methods: Flow Chart

- IPD cases,1998 ABCs*

- IPD Cases without the 23V-PPV

- Cases of IPD after vaccine use

- IPD Cases without the 23V-PPV

- assumptions

- assumptions

- Part 1

- Part 2

- *Active Bacterial Core surveillance is an active, population-based system operating in nine
- Emerging Infectious Diseases program sites (total surveillance population of 17 million in 1998)

## Vaccine Assumptions*

- *Base case, high and low sensitivity assumptions not shown

## Part 1: Projecting the impact of 23V-PPV on current IPD cases

- Apply assumptions about 23V-PPV :
-        75% VE at 65 yr (60% at 75 yr, 34% at 85 yr)
-        5 yr duration of maximum protection
-        46% vaccinated at 65 yr
-       (for part 1 only we assumed that 8% of 75yr old
-        and 7% of 85 yr old persons were also vaccinated)

- IPD Cases, 1998 ABCs
- Race-adjusted, serotype-specific,
- age group-specific IPD rates

- IPD Cases without the 23V-PPV

## Estimated cases of IPD prevented by the 23V-PPV in persons 65 in the US

- 						           _ __IPD_           _Cases/yr_
- Estimated 1998 ABCs rate :   		59.8/ 105 	20,560
- in persons  65
- Estimated rate in persons  65
- without the 23V-PPV:  			68.2/ 105 	 23,480
**Current PPV use is responsible for preventing 2,900 cases (12% decrease) of IPD in elderly.**

**Notes:**
After adding back the cases prevented by the PPV, the overall rate of IPD in the elderly, if  the current PPV was not in use, is almost 65 cases/ 100,000.  

The 1998, ABCs rate of IPD among elderly persons was 60 cases/ 100,000.  

The PPV was responsible for a 7.6% decrease in IPD.

## Distribution of prevented cases of IPD by age group

**Most IPD was prevented during the first 5 years after vaccination**.

## Part 2: Projecting the impact of new vaccines on pneumococcal disease

- Apply assumptions:
-      effectiveness
-      duration of protection
-      proportion vaccinated
-      serotype coverage

- Cases of IPD without PPV

- Cases of IPD after vaccine use

## New pneumococcal vaccines

- _Polysaccharide-protein conjugate vaccines_
-           	Recently licensed or in clinical trial:
- 			- pediatric formulation 7-valent
-           		- pediatric formulation 11-valent
- 		Hypothetical:
- 			- geriatric formulation 7-valent
- 			- geriatric formulation 11-valent
- Future vaccine:  A _common antigen vaccine_ that covers all 90+ pneumococcal serotypes (e.g. PsaA, PspA, PspC, pneumolysin)

## New pneumococcal vaccines: serotype coverage

| Vaccine | Serotypes included in vaccine | Serotype coverage for elderly |
| --- | --- | --- |
| 7V-pediatric conjugate | 4, 6B, 9V, 14, 18C, 19F, 23F | 56% |
| 11V-pediatric conjugate | 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 7F | 65% |
| 7V-geriatric conjugate | 3, 4, 6B, 9V, 14, 22F, 23F | 60% |
| 11V-geriatric conjugate | 3, 4, 6B, 9V, 14, 22F, 23F, 11A, 12F, 18C, 19F | 72% |
| Common antigen | all | 100% |

## Comparing effect of different vaccine formulations and strategies on preventing pneumococcal disease

## Effect of duration of protection in new vaccines on preventing IPD

**If new vaccines had a duration of protection longer than the 23V-PPV (i.e. longer than 5 years maximum protection, 15 years of waning protection) they would prevent more disease than the 23V-PPV**

- 10.6% decrease
-  in cases with
- 23V-PPV

**Notes:**
Duration of vaccine protection is very important.  One of the limitations of the PPV is the limited duration of protection.  
In this graph we show the impact of duration of protection on the effectiveness of the new vaccines.   
	5-10- and 15 years of maximum effectiveness are shown on the x axis.  
The percent of IPD cases prevented by the PPV is represented by this line.  

	If the new vaccines only had 5 years of maximum protection, similar to the PPV, they would not offer much advantage over the PPV.  
	However, because conjugate and protein vaccines induce immunologic memory , their duration of maximum protection should be greater than 5 years. 

 	With booster doses, maximum effectiveness may last 15 years or more.  If duration of maximum effectiveness is 15 years, the new vaccines prevent more cases of IPD than they would if duration was only 10 years, and many more cases than the PPV.  

	Clearly, one of the major advantages of the new vaccines, compared to the PPV, is the longer duration of maximum protection that is possible with a non-polysaccharide antigen.

## Effect of increasing vaccination level on protection against IPD

**7V, PPV**

**11V**

**com Ag**

- 2010 goal

- (overlapping)

**Doubling the proportion of elderly who are vaccinated would double the **
**amount of disease prevented for all vaccines.**

**Notes:**
Recent efforts have focused on improving PP vaccine coverage in the elderly.  The healthy person 2010 goal for PP vaccine coverage is 60%.  

In the analysis shown in this graph, we compared the decrease in IPD cases that occurs with increasing vaccine coverage for each vaccine.  

Baseline assumptions about vaccine effectiveness and duration of maximum effectiveness are similar to earlier slides. 

 Vaccine effectiveness is shown on the x axis and increases from 50% to 90%.  

Each line represents a different vaccine in the model.  
This line is the PPV and the one above it is the pediatric conjugate 7 valent vaccine.   

At the baseline vaccine coverage of 50%, the new vaccines prevent more cases of IPD than the PPV. 

In addition, notice that  the slopes of the lines for the new vaccines are greater than the slope of the line for the PPV.  Therefore,  as vaccine coverage increases, the new vaccines will prevent proportionally more cases of IPD than the PPV.   

## Effect of vaccines on preventing deaths due to pneumococcal disease

| Vaccine | # Deaths prevented
 (% decrease) |
| --- | --- |
| 23V- PPV | 394 (10.2) |
| 7V- conjugate | 390 (10.1) |
| 11V-conjugate | 464 (12.1) |
| Common antigen | 647 (16.7) |

## Sensitivity analysis: assumptions

|  | base | low | high |  | base | low | high |
| --- | --- | --- | --- | --- | --- | --- | --- |
| VE, IPD | 75% | 47% | 85% |  | 75% | 47% | 85% |
| VE, pneumonia | 0 | 0 | 50% |  | 50% | 0 | 73% |
| Duration | 5yr | 5yr | 5yr |  | 10yr | 5yrs | 15yrs |
| % vaccinated | 46% | 46% | 90% |  | 46% | 46% | 90% |

- 23V-PPV

- New vaccines

## Sensitivity analysis of VE: Percent decrease in IPD cases

|  |  | Sensitivity Analysis |  |
| --- | --- | --- | --- |
| Vaccine | Base | Low | High |
| 23V-PPV | 10.6 | 6.7 | 12.0 |
| 7V-conjugate pediatric | 10.7 | 6.7 | 12.1 |
| 11V-conjugate pediatric | 12.7 | 8.0 | 14.4 |
| Common antigen
 | 17.7 | 11.1 | 20.1 |

## Sensitivity analysis of VE: Percent decrease in non-invasive pneumococcal pneumonia cases

|  |  | Sensitivity Analysis |  |
| --- | --- | --- | --- |
| Vaccine | Base | Low | High |
| 23V-PPV | 0 | 0 | 4.9 |
| 7V-conjugate pediatric | 5.6 | 0 | 8.2 |
| 11V-conjugate pediatric | 6.5 | 0 | 12.7 |
| Common antigen
 | 10.0 | 0 | 14.7 |

## Best case scenerios

_**23V-PPV**_
- Assumptions: 85% VE IPD, 50% VE pneumonia, 90% vaccinated, 5yr duration
- Prevent:
- 5513 cases of IPD (23.5%)
- 3364 cases of non-invasive pneumonia (11.3%)
_**7V-pediatric conjugate**_
- Assumptions: 85% VE IPD, 73% VE pneumonia, 90% vaccinated, 15yr duration
- Prevent:
- 7792 cases of IPD (33.2%)
- 7110 cases of non-invasive pneumonia (23.9%)

## Best case scenerios

_**Common antigen**_
- Assumptions: 85% VE IPD, 73% VE pneumonia, 90% vaccinated, 15yr duration
- Prevent:
- 12,580 cases of IPD (53.6%)
- 12,698 cases of non-invasive pneumonia (42.8%)

## Summary of Model Results

- Conjugate vaccines may prevent more IPD and pneumococcal pneumonia than 23V-PPV despite less serotype coverage
- A common antigen vaccine may have the greatest effect on disease prevention
- Benefit of new vaccines over 23V-PPV is dependent upon longer duration of protection and efficacy against pneumonia
- Geriatric formulations of conjugate vaccines do not improve protection compared with pediatric formulations
- For all vaccines, increasing vaccine coverage would prevent more invasive disease than current coverage

## Limitations

- Unable to incorporate effects on transmission and carriage
- No data regarding conjugate or common antigen vaccine performance in adults

## Conclusions

- New pneumococcal vaccines should be evaluated for use in the elderly
- Data on duration of protection and efficacy against non-invasive pneumococcal disease are important outcomes to evaluate
- Improving vaccination levels with the licensed 23V-PPV could prevent many cases before newer vaccines are available

## Acknowledgements

- Respiratory Diseases Branch, Division Bacterial and Mycotic Diseases, NCID
- Epidemiology Section
- Laboratory Sections