Pneumococcal vaccine reduced invasive disease, lacked effect on nasal colonization

Results of a nationwide study indicate that a new conjugate vaccine is highly effective at preventing invasive pneumococcal disease in children aged younger than 2 years.

The nationwide study is the first to confirm the 93% to 100% effectiveness of the three-dose (2+1) schedule that is already used in many national programs. The pneumococcal vaccine contains 10 serotype-specific polysaccharides conjugated to Haemophilus influenzae protein D, tetanus toxoid, and diphtheria toxoid as the carrier proteins (PHiD-CV10) and is designed to provide protection against 10 of the most common pneumococcal strains in children aged younger than 5 years. The vaccine was licensed in the European Union in March 2009 (Synflorix, GlaxoSmithKline Vaccines).

“Introduced in 2000, widespread use of the first PCV7 (Prevnar, Pfizer) vaccine has significantly reduced the burden of [invasive pneumococcal disease] in children younger than 5 years. Our findings suggest that a series of three or four shots of the new PHiD-CV10 vaccine including three additional pneumococcal strains is going to work at least as well in preventing [invasive pneumococcal disease], with the potential to prevent over 70% of severe pneumococcal disease cases in children worldwide,” study researcher Arto Palmu, MD, of the department of vaccination and immune protection, National Institute for Health and Welfare, Tampere, Finland, said in a press release from The Lancet.

Vaccine effectiveness

Nearly 46,000 children aged younger than 19 months were randomly assigned to receive two to four doses of PHiD-CV10 (according to age) or hepatitis A or B vaccine as control. Researchers tracked the vaccine’s effectiveness during a mean 2-year period using the National Infectious Diseases Register.

They found that the PHiD-CV10 vaccine prevented 93% of cases of invasive pneumococcal disease in healthy infants who received at least one dose. Only one disease episode due to a serotype contained in the vaccine was detected shortly after the first vaccine dose compared with 12 in the control group. This translates to vaccine effectiveness of 92% against vaccine-type invasive pneumococcal disease for the three-dose schedule and 100% for the four-dose (3+1) schedule. No safety concerns were noted during the study.

Nasal colonization

Results of a separate PHiD-CV10 study, led by Menno R. van den Bergh, MD, found thatPCV10 had no differential effect on nasopharyngeal non-typable H. influenzae (NTHi) colonization or H. influenzae density in healthy Dutch children aged up to 2 years.

This implies the vaccine does not induce herd effects for NTHi, and other bacterial colonization patterns were also similar, according to the findings.

The randomized controlled trial, conducted in the Netherlands between April 2008 and December 2010, enrolled 780 infants who received either PCV10 or PCV7 (2:1) at 2, 3, 4 and 11 to 13 months of age.

Nasopharyngeal samples were obtained at ages 5, 11, 14, 18 and 24 months and cultured to detect H. influenzae, Streptococcuspneumoniae, Moraxella catarrhalis and Staphylococcus aureus. Polymerase chain reaction assays quantified H. influenzae and S. pneumoniae and confirmed NTHi.

In both groups, NTHi colonization increased with age, from 33% in children aged 5 months to 65% in those aged 24 months. Three months after the booster dose, vaccine effectiveness against colonization was 0.5% (95% CI, –21.8 to 18.4), and vaccine effectiveness against acquisition was 10.9% (95% CI, –31.3 to 38.9). At each sampling moment, no differences between groups in either NTHi prevalence or H. influenzae density were detected.

Colonization patterns were similar among the S. pneumoniae (range, 39%–57%), M. catarrhalis (range, 63%–69%) and S. aureus (range, 9%–30%) groups.

Questions remain

According to van den Bergh, of the department of pediatric immunology and infectious diseases at Wilhelmina Children’s Hospital and University Medical Center Utrecht in the Netherlands, and colleagues, the study findings raise the question of how this vaccine induces protection against NTHi-caused acute otitis media, but does not affect the presence of NTHi in the nasopharynx, which is generally regarded the point from which respiratory tract infections originate.

First, intervening with protein D function may not fully prevent a complex biological process such as colonization. Second, in a chinchilla model for AOM, previous studies found that abrogation of protein D’s activity reduced NTHi adherence in the middle ear, but not in the nasopharynx. This suggests, according to the study researchers, a compartment-specific effect. Third, the efficacy of PHiD-CV10’s predecessor (11Pn-PD vaccine) against NTHi AOM could merely reflect prevention of the first pneumococcal AOM.

“In addition, pneumococcal conjugate vaccination shifts colonization from vaccine to nonvaccine pneumococcal serotypes and may affect colonization with non-pneumococcal species, such as S. aureus or NTHi,” the study researchers wrote.

For more information:

Palmu AA. Lancet. 2012;doi:10.1016/S0140-6736(12)61854-6.

van den Bergh MR. Clin Infect Dis. 2012;doi:10.1093/cid/cis922.

Disclosure:The study was funded by GlaxoSmithKline Biologicals SA, manufacturer of the vaccine, and National Institute for Health and Welfare, Finland. Some of the researchers report receiving grant support from various vaccine manufacturers.