Pneumococcal conjugate vaccine: the second year and looking good

June 2001

---Philip A. Brunell, MD

Since the pneumococcal conjugate vaccine [Prevnar, Wyeth] containing 7 of the serotypes most likely to cause invasive pneumococcal disease in the United States was licensed in February 2000, more than 15 million doses have been given. The expectations of safety and efficacy based on the prelicensure clinical trials appear to be fulfilled. After licensure of any vaccine there is concern that some rare event, which was not observed before licensure, will become apparent as the number of vaccine recipients increases from 104 to 106 or 107. This does not appear to be the case with the pneumococcal conjugate vaccine (PCV7).

In preclinical trials, most of the local and febrile reactions in vaccinees could be attributed to the other vaccines given simultaneously. When given alone, only a small number of vaccinees had these reactions, usually to the fourth dose of PCV7. From the postlicensure surveillance at the Kaiser Permanente Bay Area site, seizures, SIDS or other serious adverse events do not appear to be caused by PCV7.

Efficacy data

The efficacy observed in the prelicensure studies has held up as better than 90% and has been observed whether one uses “per protocol” or “intention to treat” (includes some failures after only a single dose) data. These hold even if all pneumococci rather than only the 7 serotypes in the vaccine are considered. Most impressive, however, is the decreased incidence of invasive disease at the Permanente Bay Area site following the introduction of routine use of PCV7. There were estimated to be about 1,400 cases of meningitis and 16,000 cases of bacteremia in the United States annually in children younger than 5 years prior to licensure. A reduction of even 90 would be a significant public health achievement. This alone is sufficient reason to justify the routine use of PCV7.

The questions concerning the use of PCV7 in children older than 24 months who are not at high risk still remains problematic. However, this issue may become moot before we know the answer. After routine immunization has been in place for 24 months, one will not have to ponder what to do with those older than 24 months. When one asks the question “would a child with ‘frequent’ otitis over 24 months who has not been immunized benefit?” it is well to remember that we are talking about a single dose of a safe, albeit expensive, conjugate vaccine. The benefits in terms of otitis are apparent in the decreased likelihood of tube placement, which can be very costly, or in kids with more than 5 attacks in a single year.

It is unclear from the data we have seen how much benefit from immunization would accrue to children older than 24 months. This must be viewed in the context of the tendency for otitis to become less of a problem with increasing age without any intervention. Administration of the 23-valent polysaccharide vaccine to these children does not appear to have a dramatic effect, although it has been used by some. Whatever benefit there will be in terms of pneumonia will be minimal but an extra bonus. Although there was a 73% reduction in lobal pneumonia in those immunized, this constituted only 2.5% of all cases of clinically diagnosed pneumonia at the Kaiser Permanente Bay Area site.

Should one give PCV7 to children older than 24 months who are in out-of-home care? Children in day care are at increased risk of invasive pneumococcal disease and are more likely to be infected with resistant pneumococci. The latter is directly related to the proportion of children receiving antibiotics. The use of PCV7 has been associated with a decrease in carriage of pneumococci in day care attendees. In addition, there is a decreased carriage in their siblings. Thus, there appears to be virtue in the use of PCV7 in day care attendees, as this would be expected to produce some herd immunity.

The decrease in pneumococcal carriage in vaccinees has raised concern about replacement with non-vaccine serotypes. It is important to distinguish between replacement and revelation. That is, the ability to recognize non-vaccine serotypes, which were already present, by elimination of predominant vaccine strains by immunization. The Kaiser Permanente Bay Area site group has not found replacement in invasive disease but this will have to be watched. There may be spontaneous changes in serotypes independent of vaccine use as found in Kate O’Brien’s studies in Native Americans (see story). Serotypes certainly differ in different populations and in various parts of the world. They also differ by age. Those found in ear aspirates differ to some extent from those isolated from blood. Concern about serotype coverage, serotype changes resulting from immunization and the cost of including multiple serotypes in vaccines have stimulated interest in vaccines using antigens common to all serotypes. These may be the way of the future but for now, PCV7 is “lookin’ good.”