Contents

15 Pneumococcal disease

15.4 Vaccines

15.4.1 Available vaccines

There are two types of pneumococcal vaccine registered (approved for use) and available (marketed) in New Zealand for use against S. pneumoniae: protein conjugate pneumococcal vaccine and unconjugated polysaccharide pneumococcal vaccine. In the protein conjugate vaccines, the pneumococcal polysaccharide is coupled to a carrier protein. The protein conjugate induces increased production of antibodies, immunological memory and maturation of the antibody response (see section 1.2.3).

Funded vaccines

The S. pneumoniae vaccines funded as part of the Schedule are:
  • the 13-valent protein conjugate vaccine PCV13 (Prevenar 13, Pfizer NZ Ltd), for all children aged under 5 years as part of the usual childhood schedule and for individuals aged 5 years and older with defined high-risk conditions 
  • the 23-valent polysaccharide vaccine 23PPV (Pneumovax 23, MSD), for individuals aged 2 years and older with defined high-risk conditions.
PCV13

Each dose of PCV13 contains: 2.2 μg of pneumococcal purified capsular polysaccharides for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F and 23F, and 4.4 μg of pneumococcal purified capsular polysaccharides for serotype 6B. Each serotype is individually conjugated to non-toxic diphtheria CRM197 protein and adsorbed onto aluminium phosphate (0.565 mg). Each dose contains succinic acid, polysorbate 80, aluminium phosphate and sodium chloride in water for injections.

23PPV

23PPV includes 23 serotypes: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F. Each dose contains 25 µg of each capsular polysaccharide antigen, dissolved in isotonic saline solution, with phenol (0.25 percent) added as a preservative, and no adjuvant.

Other vaccines

The 10-valent pneumococcal conjugate vaccine previously used on the Schedule is still registered and available in New Zealand.

15.4.2 Efficacy and effectivenessTop

13-valent pneumococcal conjugate vaccine (PCV13)

Immunogenicity

Immunogenicity studies for PCV13 showed high levels of functional antibody not inferior to those induced by PCV7 for the common serotypes, and a comparable antibody response for the additional serotypes (including 19A).24–27

Impact on nasopharyngeal colonisation

A randomised double-blind trial in healthy infants compared the impact of PCV13 versus PCV7 on nasopharyngeal colonisation and immunogenicity.28 Infants were randomised to receive either PCV7 or PCV13 at ages 2, 4, 6 and 12 months. PCV13 significantly reduced nasopharyngeal colonisation of the additional PCV13 serotypes 1, 6A, 7F and 19A; the cross-reacting serotype 6C; and the common PCV7 serotype 19F. It was comparable with PCV7 for all other common serotypes, except for serotype 5 where there were too few events to draw inference. Following the introduction of PCV13, reductions in nasopharyngeal colonisation by vaccine serotypes have been seen in early observational data from Alaska,29 Italy30 and France (in children with acute otitis media).31

PCV13 effectiveness

In an open-label clinical trial, Alaskan native children aged under 5 years were offered PCV13 as appropriate for age and prior history of PCV7 vaccination.32 Following the introduction of PCV13, IPD caused by PCV13 serotypes declined significantly from 31 to 7 cases. No cases of IPD caused by PCV13 serotypes occurred among children who received PCV13 vaccine (3680 person-follow-up years). There were seven PCV13 serotype cases among children who had not received the vaccine (5007 person-follow-up years). There were 52 all-type IPD cases in the study population in the period before the study (399 per 100,000) and nine cases after the study commenced (107 per 100,000).

Early data from the UK suggests that in children aged under 2 years, IPD due to PCV13 serotypes had halved one year after the vaccine was introduced.33 Similarly, following the introduction of PCV13 vaccine in Norway,21 the US34 and Canada,22 early data indicates reductions in IPD caused by PCV13 serotypes.

PCV7 was introduced to the Apulia region in Italy in 2006 and was replaced by PCV13 in 2010.35 Comparing hospitalisation risk ratios for the pre-PCV years to the vaccination period, PCV effectiveness against vaccine-type IPD was 84.3 percent (95% CI: 84.0–84.6). There was an overall reduction in the number of pneumococcal disease-related hospitalisations, particularly for pneumococcal pneumonia (RR: 0.43, 95% CI: 0.21–0.90).

In the United States, PCV7 was licensed in 2000 and PCV13 in 2010. In a study of claims data for otitis media visit rates and related complication rates in children aged 6 years or younger, there was an overall downward trend in otitis media-related healthcare visits from 2001 to 2011.36 In children aged under 2 years, there was a significant reduction in otitis media visit rates in 2010–2011, which coincided with the availability of PCV13.

Use of pneumococcal conjugate vaccines in older children and adults

PCV13 is safe and immunogenic when administered to healthy older children, regardless of previous PCV7 vaccination.37 In the US and Europe, PCV13 licensure was extended in 2013 to older children aged 6–18 years. One dose is recommended in the US for children at risk of pneumococcal disease.38 In New Zealand, PCV13 licensure was extended in 2015. PCV13 is now registered for all individuals aged 6 weeks and older.

There is little data on the effectiveness of pneumococcal conjugate vaccines in adults. PCV13 is immunogenic in adults aged over 50 years,39 including adults aged over 70 years.40 It is at least as immunogenic as 23PPV. Some studies suggest that 23PPV attenuates the immune response to subsequent doses of PCV13.40, 41 This attenuation is not seen if PCV13 is given before 23PPV.

Based on immunogenicity data, pneumococcal conjugate vaccines are likely to be effective at preventing pneumococcal disease in older children and adults, but data from ongoing clinical trials is needed before the precise role of these vaccines is defined for adults. However, priming adults with conjugate vaccines prior to any doses of 23PPV vaccine seems well supported.

Pneumococcal polysaccharide 23-valent vaccine (23PPV)

The polysaccharide vaccine (23PPV, Pneumovax 23) is made from the purified capsular polysaccharide antigens of 23 serotypes of S. pneumoniae. It is available in New Zealand for adults and children from age 2 years. 23PPV includes the 23 serotypes (see Table 15.1) responsible for about 90 percent or more of cases of invasive disease in developed countries.

23PPV efficacy

Assessment of the efficacy of pneumococcal vaccination depends on whether immune-competent or immune-compromised patients are studied, and whether the end point is pneumococcal pneumonia or bacteraemia.

The problems with the polysaccharide vaccine have been summarised as:

Although it is generally accepted that 23PPV is effective at preventing IPD in immune-competent adults, a 2009 meta-analysis concluded that in trials of high quality, there is no evidence of vaccine protection against IPD and that 23PPV may not be protective against either IPD or pneumonia.42 A subsequent case-control study in patients aged over 60 years concluded that 23PPV provided a significant protective effect against IPD in elderly immune-competent patients.43 However, a 2012 review of data from elderly populations concluded that that low protection was possible but differences in study designs prevent definitive conclusions.44

15.4.3 Transport, storage and handlingTop

Transport according to the National Guidelines for Vaccine Storage and Distribution.45 Store at +2oC to +8oC. Do not freeze.

15.4.4 Dosage and administrationTop

The dose of PCV13 and 23PPV is 0.5 mL, administered by intramuscular injection (see section 2.3). 23PPV can also be administered by subcutaneous injection (see section 2.3), but there is an increased likelihood of injection site reactions.46 (See also section 1.4.2).

Co-administration with other vaccines

PCV13 or 23PPV may be administered at the same time as other routine childhood vaccinations, in a separate syringe at a separate injection site (see section 2.3). The exception is the quadrivalent meningococcal conjugate vaccine MCV4-D, which should be given at least four weeks after PCV13. (See section 12.4.4).

PCV13 has been associated with increased risk of fever over 39oC and febrile convulsions when co-administered with inactivated influenza vaccine in children aged 6–59 months. Separation of the vaccines by two days can be offered, but is not essential. Systemic reactions have been noted in adults aged over 65 years. (See sections 15.6.2 and 15.7.2).

Following an analysis of post-marketing reporting rates, there is a potential increased risk of convulsions (with or without fever) and hypotonic-hyporesponsive episodes when co-administering DTaP-IPV-HepB/Hib (Infanrix-hexa) and PCV13 compared to the use of DTaP-IPV-HepB/Hib alone.47–51 (See section 15.7.2.)

Recent evidence52 suggests that herpes zoster vaccine can be concomitantly delivered with 23PPV, despite earlier research to the contrary. (See section 22.4.4).