Pneumococcal vaccine

Pneumococcal polysaccharide vaccine

The question of whether revaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) at least 5 years after the first vaccination is associated with more frequent or more serious adverse events than those after the first vaccination has been studied in patients aged 50–74 years who had never been vaccinated with PPV (n = 901) or who had been vaccinated once at least 5 years before enrolment (n = 513) [ ]. After one dose of PPV, local injection site reactions and prevaccination concentrations of type-specific antibodies were measured. Those who were re-vaccinated were more likely than those who received their first vaccinations to report a local injection site reaction of at least 10.2 cm (4 in.) in diameter within 2 days of vaccination (55/513 versus 29/901, or 11% versus 3%). The reactions resolved by a median of 3 days after vaccination. The highest rate was among revaccinated patients who were immune competent and did not have chronic illnesses: 15% (33/228) compared with 3% (10/337) among comparable patients receiving their first vaccinations. The risk of these local reactions correlated significantly with prevaccination geometric mean antibody concentrations. The authors concluded that physicians and patients should be aware that self-limited local injection site reactions occur more often after revaccination compared with a first vaccination; however, this risk does not represent a contraindication to revaccination with PPV in recommended patients.

Pneumococcal conjugated polysaccharide vaccines

Pneumococcal polysaccharides are not immunogenic in infants, but improved immunogenicity of polysaccharide-protein conjugates has been demonstrated. One of the major problems in developing a successful vaccine against S . pneumoniae is the large number of different serotypes involved. More than 83 serotypes of the bacterium are known to cause disease, although about 10 of these account for up to 70% of disease in young children. The frequency of the serotypes can vary from year to year, from one age group to another, and from place to place. Various conjugated vaccines that include different serotype variations are already licensed (the heptavalent conjugated vaccine Prevnar/Prevenar), under development or undergoing clinical trial (9- and 11-valent conjugated vaccines). If the vaccines prove to be successful, it is estimated that their use could reduce child deaths from pneumococcal pneumonia by up to 25%, saving over 250 000 lives a year worldwide. The development of conjugate pneumococcal vaccines has also been driven by the high incidence of inner ear infections and the severity of meningitis due to S . pneumoniae in industrialized countries. The results of some clinical trials with different vaccines of this type have been reviewed [ , ].

The immunogenicity of 7-valent pneumococcal-conjugate vaccine plus 23-valent pneumococcal vaccine in 11 children has been compared with the immunogenicity of 23-valent vaccine alone in 12 children up to 2 years of age with sickle cell disease [ ]. IgG pneumococcal antibody concentrations were higher with combined administration, with no increase in adverse reactions after vaccination with 23-valent vaccine.

In 2000, the first heptavalent conjugated pneumococcal vaccine, Prevnar, which contains polysaccharides of pneumococcal serotypes 4, 6B, 9V, 14, 19F, and 23F, and oligosaccharide of serotype 18C, conjugated to the protein carrier CRM 197 (non-toxic variant of diphtheria toxin), was licensed in the USA (covering 90% of pneumococcal serotypes found in young children in the USA) and in all EU member states, as well as in selected other countries in 2001. In a randomized, double-blind study, 302 healthy infants in the Northern California Kaiser Permanente Health Plan received either the pneumococcal vaccine or meningococcal group C conjugate vaccine as a control at 2, 4, and 6 months of age and a booster at 12–15 months of age [ ]. Immunogenicity and adverse reactions after simultaneous administration of vaccines used in the routine immunization program of children (DTwP or DTaP, Hib and OPV or hepatitis B vaccine) were also evaluated. Local reactions after pneumococcal, DTwP-Hib, and DTaP plus Hib vaccine were statistically less severe at the pneumococcal vaccine site than at the DTwP-Hib sites ( Table 1 ). There were 12 emergency room visits and 8 hospitalizations that occurred soon after immunization (otitis, febrile illness, urinary tract infection, burns), but none was thought to be related to the vaccine. One hypotensive-hyporesponsive episode 15 minutes after pneumococcal vaccine, DTwP-Hib/HB, and OPV, with complete recovery within 1 hour, was considered to have been vaccine-related. After the booster dose of pneumococcal vaccine, the geometric mean titers of all seven serotypes increased significantly (compared with the values after dose 3 and before dose 4) to antibodies considered as protective. When vaccine was administered at the same time as the booster dose of DTaP and Hib vaccines, there were lower antibody titers for some of the antigens than the antibody response when the pneumococcal vaccine was given separately. Because the geometric mean titers of the booster responses were all generally high and all subjects achieved similar percentages above predefined antibody titers, these differences were considered to be probably not clinically significant. Summarizing their results the authors concluded that the pneumococcal vaccine was safe and immunogenic.

A comprehensive technical overview on the epidemiology and prevention of pneumococcal disease, including the use of polysaccharide and conjugate vaccines has been provided [ ].

There have been reports of field trials on the immunogenicity and efficacy of heptavalent conjugated pneumococcal vaccine and adverse reactions to it have appeared. Between October 1995 and August 1998, 37 868 infants were included in a double-blind trial [ ]. At 2, 4, 6, and 12–15 months of age they were randomly assigned to receive either the pneumococcal conjugate vaccine or meningococcal conjugate vaccine. More than 95% of pneumococcal vaccine recipients developed 0.15 μg/ml antibodies against all serotypes included in the vaccine. As of April 1999, a vaccine efficacy of 97% (prevention of invasive pneumococcal disease caused by vaccine serotypes) was calculated; in addition, there was a significant impact on otitis media. Data on reactogenicity of the conjugate pneumococcal and meningococcal vaccines are provided in Tables 2 and 3 . Local reactions were analysed separately for children who had received DTaP and DTwP vaccine simultaneously. Local and systemic reactions were generally relatively mild with either vaccine, and more severe local and systemic reactions were uncommon and self-limiting. There were significant differences in outpatient clinic visits for seizures (11 pneumococcal vaccine recipients versus 23 controls), but none of the subcategories of seizure (febrile seizures, epilepsy, afebrile seizures) was significantly different. There were four cases of sudden infant death syndrome (SIDS) (0.2/1000) in the pneumococcal vaccine group and eight in the controls (0.4/1000). This rate is similar to the rate of 0.5/1000 children observed in the general infant population of California.

Conjugated pneumococcal vaccines have been reviewed, including studies with experimental tetravalent and pentavalent conjugated vaccines and vaccines conjugated to various proteins [ ].

The first heptavalent conjugate pneumococcal vaccine, Prevnar (containing polysaccharides of pneumococcal serotypes 4, 6B, 9V, 14, 19F, and 23F, and oligosaccharide of serotype 18C, conjugated to the protein carrier CRM197, a non-toxic variant of diphtheria toxin), was licensed in the USA in 2000, and in all EU member states as well as in selected other countries in 2001. The efficacy, immunogenicity, and safety of conjugated pneumococcal vaccine have been evaluated in 1756 low birth weight infants (under 2500 g) and 4340 preterm infants (before 38 weeks) compared with infants of normal birth weight and infants born at full term [ ]. Vaccine efficacy was 100% in both groups. Fever and local events were similar when adjusted for clustering among multiple doses per child. After dose 3, there was more redness and swelling in infants of low birth weights and more swelling in preterm infants.

A hendecavalent pneumococcal conjugate vaccine (including serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F) was given to 117 Finnish and 135 Israeli infants at ages 2, 4, 6, and 12 months together with other vaccines used in the respective national immunization programs [ ]. The authors concluded that the vaccine is safe and immunogenic in infants. There were no severe adverse reactions. After each dose 30% of the vaccinees had local reactions, of which pain was the most common. Fever ≥ 38 °C was reported in 33–53% and a high fever (≥ 40 °C) was reported six times.

23-valent pneumococcal polysaccharide vaccine

The efficacy of polysaccharide vaccine in preventing invasive pneumococcal disease, pneumonia, and death has been assessed in a double-blind, randomized, placebo-controlled trial in 1392 HIV1-infected adults in Uganda [ ]. The vaccine was well tolerated. However, it was ineffective and is not recommended for use in HIV1-infected individuals. Reassessment of recommendations for polysaccharide vaccine immunization may be necessary in some countries. The authors suggested that the vaccine causes destruction of polysaccharide-responsive B cell clones.

In another clinical trial the immunogenicity and safety of polysaccharide vaccine has been assessed in 21 renal transplant recipients [ ]. Protective antibody titers were reached at 6 and 12 weeks after immunization in all recipients, bar one. No local or systemic adverse effects were observed.