The evidence for use of pneumococcal conjugate over polysaccharide in children

Abstract

Pneumococcal glycoconjugate vaccines are now used in infant immunization schedules, globally. Pneumococcal polysaccharide vaccines are still, however, advised from the second year of life to provide broader serotype coverage. The use of these polysaccharide vaccines has been under review, especially for children.

Keywords: :

• Pneumococcal
• conjugate
• polysaccharide
• vaccine

Since September 2006, pneumococcal glycoconjugate vaccines (PCV) have been incorporated into the UK infant immunization schedule. The 7-valent PCV (PCV7) has been demonstrated to be highly efficacious under the UK 2, 4, and 12 mo schedule with effectiveness of 93% (95% CI 70 to 98).¹ These vaccines are also currently recommended for those at increased risk of pneumococcal infection and to provide optimal serotype coverage to those at increased risk of disease. From April 2010, PCV7 was replaced with PCV13. The 23-valent polysaccharide vaccine (PPV23) is also advised in those at increased risk of pneumococcal infection from two years of age to provide broader serotype coverage. Glycoconjugate vaccines have many advantages over polysaccharide vaccines including excellent immunogenicity in infants and young children, induction of high avidity antibodies and the induction of immune memory. The use of pneumococcal polysaccharide vaccines is the topic of much debate, especially in young children.²

Antibody responses to PPV23 mature with age and tend to be higher in children from developing countries. When considering PPV23, some protection against invasive pneumococcal disease (IPD) is possible. Studies have concluded an effectiveness of approximately 60% but none are recent or of high quality. However, unlike for PCV, no effect on carriage or on acute otitis media has been reported.³

One concern is that following vaccination with PPV23 in persons primed with PCV, there is a theoretical risk of the depletion of memory B-cells to the serotypes contained within PCV, however, the clinical significance of this is currently unknown. It is known that children who have had invasive pneumococcal disease are sometimes unable to respond to their infecting serotype following PCV and that pneumococcal carriage can blunt the response to PCV to the specific serotype.² This risk of B-cell depletion is increased if revaccination with PPV23 occurs. No studies have been published in children following repeat PPV23 with intervals longer than 12 mo or in children older than 24 mo.

One of the huge benefits of PCV is the induction of herd protection though the prevention of acquisition of carriage. The benefits of herd protection have been clearly demonstrated with significant reductions in PCV serotypes in those over 5 y of age who had not received PCV vaccination.⁴ This has therefore led to a reduction in PCV serotypes in all age groups. However, in reducing carriage of PCV serotypes, this opens a niche for non-PCV serotypes, known as replacement. Key serotypes showing replacement were 7F, 19A, and 22F.⁴ Those with co-morbidities are unfortunately more vulnerable to replacement disease with less invasive serotypes not in PCV. Therefore, the benefits of vaccinating against non-PCV serotypes has increased and thus, the benefit of PPV23.

Whether the immune response to PPV23 in at-risk children is sufficient or not to confer clinical benefit depends on a number of factors which include age, underlying disease and the immunogenicity of individual serotypes. A small number of studies have been reported on the immunogenicity of PPV23 in children with recurrent infections but results from these are inconclusive as this risk group contains both immunocompetent and immunodeficient children. Two studies were performed in pediatric cardiac patients, one showing PPV23 to be immunogenic, the other not, this discrepancy may be due to the patients’ heterogeneity in time since transplant/immune suppression regime. In children with sickle cell or renal disease, PPV23 was shown to be immunogenic. Very scanty data exists concerning the immunogenicity of PPV23 in HIV infected children receiving HAART. These data indicate some evidence of immunogenicity of PPV23 in this clinical risk group.

Given the theoretical risk of memory B-cell depletion following vaccination with PPV23, it is not clear how best to maintain protection in those children at increased risk of pneumococcal infection but the potential advantages of PPV23 vaccination outweigh the potential concerns.

Disclosure of Potential Conflicts of Interest

No conflicts to declare.