Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
0.5 mL suspension in pre-filled syringe
Approved indication: prevention of Streptococcus pneumoniae infections
Australian Medicines Handbook section 20.1
This vaccine is indicated for the prevention of invasive pneumococcal disease (including pneumonia and acute otitis media) in children aged 6 weeks to 2 years. The current conjugate vaccine for this age group contains polysaccharides from seven S. pneumoniae serotypes (4, 6B, 9V, 14, 18C, 19F and 23F), whereas this new vaccine contains an additional three serotypes (1, 5 and 7F). Most of the polysaccharides in the new vaccine are conjugated to protein D (a conserved Haemophilus influenzae surface protein) rather than diphtheria toxoid which is used in the current vaccine.
The World Health Organization (WHO) has recommended that approval of pneumococcal vaccines for invasive disease can be based on immunogenicity data alone rather than efficacy trials. New vaccines should be non-inferior to the current seven-valent pneumococcal vaccine. Based on efficacy studies, the WHO has defined an antibody threshold which correlates to protection. This antibody must also be able to opsonise S. pneumoniae and promote phagocytosis by immune cells.
The new vaccine was found to be non-inferior to the seven-valent vaccine in an immunogenicity trial of 1650 babies. They were given three intramuscular doses before the age of six months and antibody titres in sera were measured a month after the last injection. An increase in titres was seen after a booster at 12 months indicating that babies had developed immune memory to the polysaccharides.1 (Antibody data for serotypes 1, 5 and 7F could not be compared to the seven-valent vaccine.)
Protection against acute otitis media is more difficult to achieve than protection against invasive infections. In a trial of 4968 babies, an eleven-valent experimental vaccine containing the ten serotypes of this new vaccine conjugated to protein D was compared to a control vaccine for hepatitis A. After vaccination (at 3, 4, 5 and 12-15 months), efficacy against acute otitis media during the follow-up period was 58% for vaccine serotypes, and efficacy against ear infections caused by non-typeable H. influenzae was 35%.2 Although not significant, the incidence of recurrent ear infections and the number of children needing grommets were less in the pneumococcal vaccine group.
When given at the same time, the pneumococcal vaccine did not affect the immunogenicity of a combined vaccine against hepatitis B, diphtheria, tetanus and acellular pertussis, H. influenzae type b and poliomyelitis.2 About 40% of infants had injection-site reactions after the vaccination. Irritability and mild fever were also common and can be treated with an antipyretic drug.3
The vaccine should be given by intramuscular injection, so caution is urged in children with thrombocytopenia or coagulation disorders because of the risk of bleeding. The safety and efficacy of this vaccine has not been established in children who have an increased risk of pneumococcal infections such as those with sickle cell disease, splenic dysfunction, HIV, malignancy or nephrotic syndrome.
The vaccine should not be withheld or delayed in premature babies, but their respiration should be monitored for 2-3 days after the first vaccination. Antibody responses in immunocompromised children may be reduced.
This vaccine should be given to infants at 2, 4 and 6 months (in the thigh), with a booster at 12 months (in the upper arm). As with the current pneumococcal vaccine, it can be co-administered with other vaccines recommended in the Australian immunisation schedule.
Based on immunological data, this vaccine should protect most babies from invasive pneumococcal disease such as pneumonia, bacteraemia and meningitis caused by the vaccine serotypes. The vaccine was efficacious against acute otitis media, but it is not known if it will be any better than the current vaccine, or how it will perform in communities where uncommon serotypes have become more prevalent.4 Because this vaccine contains protein D from H. influenzae, it should offer some protection against ear infections caused by non-typeable H. influenzae.
The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
- Vesikari T, Wysocki J, Chevallier B, Karvonen A, Czajka H, Arsne JP, et al. Immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared to the licensed 7vCRM vaccine. Paediatr Infect Dis J 2009;28:S66-76.
- Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet 2006;367:740-8.
- Prymula R, Chlibek R, Splino M, Kaliskova E, Kohl I, Lommel P, et al. Safety of an 11-valent pneumococcal vaccine conjugated to non-typeable Haemophilus influenzae-derived protein D in the first 2 years of life and immunogenicity of the co-administered hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio virus, Haemophilus influenzae type b and control hepatitis A vaccines. Vaccine 2008;26:4563-70.
- Marsh RL, Smith-Vaughan H, Beissbarth J, Hare K, Kennedy M, Wigger C, et al. Molecular characterisation of pneumococcal serotype 16F: Established predominant carriage and otitis media serotype in the 7vPCV era. Vaccine 2007;25:2434-6.