Pneumoccoccal Vaccines

There are currently four pneumococcal vaccines available in Australia. These vaccines protect against disease caused by Streptococcus pneumoniae. While asymptomatic nasopharyngeal carriage can occur, S. pneumoniae is thought to be responsible for at least one million deaths around the world each year. S. pneumoniae can cause severe invasive disease, including meningitis, pneumonia and bacteraemia, as well as non-invasive disease, such as otitis media.

The polysaccharide capsule of S. pneumoniae is a major virulence factor which allows the bacteria to evade host immune responses. While there are over 100 known serotypes, only a small number of these are responsible for the majority of pneumococcal disease. Serotypes 1 and 19A are the predominant causes of invasive disease, although serotypes 4, 5, 7F, 8, 12F, 14, and 18C are also commonly implicated. Non-bacteraemic pneumonia in adults is most commonly associated with serotype 14.

The introduction of vaccines against the most clinically relevant serotypes has led to a significant reduction in pneumococcal disease globally. However, this has led to a relative increase in the prevalence of non-vaccine serotypes.

The Australian Immunisation Handbook recommends pneumococcal vaccination for the following groups:

• Infants and children;
• Non-indigenous adults ≥ 70 years of age
• Aboriginal and Torres Strait Islander adults ≥ 50 years of age; and
• Children, adolescents and adults with risk factors for pneumococcal disease.

Risk conditions for pneumococcal disease include a previous episode of invasive pneumococcal disease, immunocompromising conditions, cerebrospinal fluid (CSF) leak, chronic respiratory disease, chronic kidney disease, chronic liver disease, cardiac disease, extremely premature birth, trisomy 21, diabetes, smoking, and harmful use of alcohol. Not all individuals with a risk condition for pneumococcal disease are eligible to receive a dose funded by the National Immunisation Program (NIP).

Pneumococcal vaccines can be divided into two types: pneumococcal conjugate vaccines (PCV) and pneumococcal polysaccharide vaccines (PPV). Both vaccine types contain antigenic polysaccharides from pneumococcal serotypes that commonly cause disease.

Pneumococcal conjugate vaccines

The polysaccharides in PCVs are attached to a carrier protein in order to increase their immunogenicity. The carrier protein used is a non-toxic variant of diphtheria toxin known as CRM₁₉₇ protein. A single mutation of the diphtheria toxin eliminates its toxicity while retaining its immunostimulant properties.

The immune response to the bacterial polysaccharide is a T-cell-independent process. However, conjugation to the CRM₁₉₇ protein modifies this response to be T-cell-dependent. This results in a stronger immune response and the generation of memory B-cells. Pneumococcal conjugate vaccines also reduce asymptomatic carriage of the vaccine serotypes, which may provide indirect protection for unvaccinated people.

The PCVs available are:

• Prevenar® 13
  • 13-valent (13vPCV)
  • 2.2µg of pneumococcal purified capsular polysaccharides for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F and 23F
  • 4.4µg of pneumococcal purified capsular polysaccharides for serotype 6B
  • Indicated for use in people from 6 weeks of age and older
• Prevenar® 20
  • 20-valent (20vPCV)
  • 2.2µg of pneumococcal purified capsular polysaccharides for serotypes 1, 3, 4, 5, 6A, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F
  • 4.4µg of pneumococcal purified capsular polysaccharides for serotype 6B
  • Approved indication has recently been extended to include infants and children from 6 weeks of age
• Vaxneuvance®
  • 15-valent (15vPCV)
  • 2.0µg of pneumococcal purified capsular polysaccharides for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F
  • 4.0µg of pneumococcal purified capsular polysaccharides for serotype 6B
  • Indicated for use in people from 6 weeks of age and older

Prevenar® 20 and Vaxneuvance® are considered extended valency vaccines as they cover more serotypes than Prevenar® 13. However, these newer vaccines are not currently covered on the NIP.

Pneumococcal polysaccharide vaccine

Pneumovax® 23 contains the purified capsular polysaccharides from 23 of the most prevalent or invasive S. pneumoniae types, including the six serotypes most commonly responsible for antibiotic-resistant pneumococcal infections. According to surveillance data from the United States, this vaccine covers at least 90% of pneumococcal blood isolates and around 85% of all pneumococcal isolates found at sites generally considered sterile.

The immune response to this vaccine is primarily an IgM response with some contribution from IgG. Protective antibodies are generated without the involvement of T-cells, resulting in a less robust response and a shorter duration of immunity compared to conjugated vaccines. Immunocompromised adults and children younger than two years of age are also likely to respond poorly to this vaccine. However, when a PCV is used as the priming vaccine, the immunologic response to subsequent doses of a PPV is significantly greater.

Pneumovax® 23:

• 23-valent (23vPPV)
• 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
• May be used in people ≥ 2 years of age (poor immune response in younger individuals)
• May be given by intramuscular or subcutaneous injection. The intramuscular route is preferred to minimise injection site reactions.

The recommendations for 23vPPV administration have changed and it is no longer recommended for healthy non-Indigenous adults aged 70 years or older. This vaccine is still recommended for Aboriginal and Torres Strait Islander adults aged 50 years or older and adults with risk conditions. This advice follows trial data showing that conjugate vaccines are effective in older adults for the prevention of vaccine-type pneumococcal pneumonia and invasive pneumococcal disease. According to Australian data, most disease caused by the additional serotypes contained in 23vPPV occurs in Indigenous adults and individuals with risk conditions. Therefore, the 23vPPV is now only offered to those groups.

The serotypes contained in each of these vaccines are shown in Table 1.

Table 1. Serotypes covered by each pneumococcal vaccine

Vaccine recommendations:

While the optimal vaccine schedule is presently under review in Australia, the current recommendations from the Australian Immunisation Handbook are:

• Universal childhood schedule
  • All non-Indigenous children, and Aboriginal and Torres Strait Islander children living in ACT, NSW, Tasmania and Victoria
  • Three doses of pneumococcal conjugate vaccine
  • Doses at age 2 months, 4 months and 12 months.
• At-risk children 12 months or under
  • All children with risk conditions, and Aboriginal and Torres Strait Islander children living in NT, Qld, SA and WA
  • Four doses of pneumococcal conjugate vaccine and two doses of 23vPPV
  • Conjugate vaccine at 2 months, 4 months, 6 months and 12 months.
  • 23vPPV at 4 years with a second dose at least 5 years later.
• Children over 12 months, adolescents and adults of any age diagnosed with a risk condition
  • Single dose of conjugate vaccine at diagnosis
  • Then two doses of 23vPPV (first dose 12 months after 13vPCV or at age 4 years, whichever is later, then second dose at least 5 years later).
• Aboriginal and Torres Strait Islander adults aged ≥ 50 years
  • Single dose of conjugate vaccine and 2 doses of 23vPPV (first dose 12 months after conjugate vaccine, and second dose at least 5 years later).
• Non-Indigenous adults aged ≥ 70 years
  • Single dose of conjugate vaccine

Additional resources:

• Australian Immunisation Handbook
• National Immunisation Program schedule
• Department of Health and Aged Care – risk conditions for pneumococcal disease and their eligibility for NIP funding