New pneumococcal vaccine effective against nasopharyngeal carriage

June 2001

BALTIMORE — Results of the first study to demonstrate that the pneumococcal 7-valent conjugate vaccine (PCV7, Prevnar, Wyeth Lederle Vaccines) provides direct protection against nasopharyngeal carriage of vaccine-type Streptococcus pneumoniae were presented here at the 2001 Pediatric Academic Societies Annual Meeting.

The study involved a high-risk population — Native American infants. Apache and Navajo infants between 7 and 12 months received 3 doses of either pneumococcal conjugate vaccine or a control vaccine (meningococcal C conjugate) as part of a large community randomized efficacy trial. The investigators collected nasopharyngeal swabs at 3 separate intervals: 1 month following the 3-dose primary series (7-12 months), at the booster dose (12-15 months), and at 6 months after the booster dose (18-21 months). Nasopharyngeal samples were tested for serotype-specific Streptococcus pneumoniae using a novel and highly sensitive immunoblot method, according to Katherine L. O’Brien, MD, an assistant research professor at The Johns Hopkins University School of Public Health here.

In total, 577 vaccinees from 513 households were enrolled in the study between February 1998 and April 1999, and followed through May 31, 2000. Serotype-specific S. pneumoniae was recovered from 62.7% of 303 infants who received PCV7 and 64.4% of 274 infants who received the control vaccine.

“Among colonized infants, those immunized with Prevnar were less likely to carry a vaccine-type strain: 23.7% vs. 35.5%,” said O’Brien, the study’s lead investigator. “However, the children immunized with Prevnar were more likely to carry a non-vaccine-type strain.” The relative risk for these children was 1.2.

“The importance of this finding biologically is at the moment unknown,” O’Brien admitted.

Still, a Finnish study of otitis media (OM) in children concluded there is an increase in disease from non-vaccine-type carriage. “But to date, there have been no other studies that have shown an increase of disease from non-vaccine-type pneumococci,” O’Brien said.

Unanswered questions

O’Brien said it was “an open question whether or not we will get increases in the rate of non-vaccine-type diseases, such as pneumonia, either bacteremic pneumonia or non-bacteremic pneumonia. And we certainly don’t know whether it will occur for invasive disease.” If PCV7 leads to invasive disease, “will the increase rate of non-vaccine-type pneumococcus be equal to the reduction in the rate from vaccine-type pneumococcus?” O’Brien posed.

The Finnish study found that the increase in non-vaccine-type OM was smaller than the reduction in vaccine-type disease. “So the overall OM rate went down,” O’Brien said. “But no one has any idea whether we will see a similar phenomenon for other mucosally related diseases like sinusitis or pneumonia, or whether it will be seen at all for invasive disease.”

In any event, “As we move forward with the introduction of conjugate vaccines into populations, everyone agrees that it is very important to conduct surveillance for the diseases that pneumococcus causes,” O’Brien noted. “We also need to conduct ongoing surveillance for nasopharyngeal colonization because the pneumococcus, when it causes disease, is coming from pneumococci carried in the nasopharynx. The effect of the vaccine on nasopharyngeal carriage is absolutely critical to anticipate the effects of the vaccine on disease.”

Changing serotypes

For example, one may encounter capsular serotype switching. “We know that the pneumococcus can change its capsule,” O’Brien said. Likewise, “we may see the emergence of new serotypes that have never previously been described. If we wait to observe those phenomenon among episodes of invasive disease, we have probably waited too long. Nasopharyngeal studies will probably allow us to observe these things months to years earlier.”

In short, “although the intention of the outcome with Prevnar is for invasive disease, as well as non-invasive disease, the mechanism for reductions in disease really relates to how it affects the nasopharynx, too,” O’Brien said. The study found the vaccine effective as early as 7 months, following the 3 doses,” she said.

“Navajo and Apache Indian children are 5 times more likely to have serious pneumococcal infections compared to other children in the United States,” O’Brien said. “We feel our results are translatable and should be translatable to other groups that are at high risk, such as children in day care and African-American children.”

For more information:

• O’Brien KL, Bronsdon M, Carlone GM, et al. Effect of a seven valent pneumococcal conjugate vaccine on nasopharyngeal (NP) carriage among Native American infants. Paper 1463. Presented at the Pediatric Academic Societies 2001 Annual Meeting. April 28-May 1, 2001. Baltimore.
• Shinefield RH, Black SB, Lewis E, et al. Efficacy of seven valent pneumococcal conjugate vaccine in premature and low birth weight infants. Paper 1465. Presented at the Pediatric Academic Societies 2001 Annual Meeting. April 28-May 1, 2001. Baltimore.

• Katherine L. O’Brien, MD, is a paid consultant for Wyeth Lederle, and has a direct financial interest in Prevnar.