Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - 49th Annual Meeting of the Infectious Diseases Society of America (IDSA)

Boston, Massachusetts / October 20-23, 2011

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

As a conjugate vaccine, 13-valent pneumococcal conjugate vaccine (PCV13) converts the T-cell-independent response elicited by free-polysaccharides to a T-cell-dependent response, explained Dr. Lisa Jackson, Group Health Research Institute, Seattle, Washington. The different type of response has been posited to establish an immunologic state more favourable to revaccination, resulting in a more robust immune response as compared with PPSV23.

“Therefore, repeated administration of PCV13 at intervals of several years may allow the immune response to the vaccine serotypes to be preserved in older adults,” Dr. Jackson noted in the introduction to her presentation (LB-3) at IDSA. “In addition, PCV13 could be administered to adults previously vaccinated with PPSV23.”

Revaccination Strategies

Investigators put the hypothesis to the test in an extension phase of a randomized clinical trial that compared PCV13 and PPSV23 in adults aged 50-64. The extension examined the response to repeat vaccination 3-4 years after the first and had 2 primary objectives: to compare the response to PPSV23 in patients ages 60-64 who initially received PCV13 with responses in patients who were randomized to PPSV23; and to compare response to PPSV23 after initial vaccination with PCV13 with response to repeat vaccination with PPSV23 administered 3-4 years after initial vaccination with PPSV23.

Response was based on geometric mean titres (GMT) as determined by opsonophagocytic assay (OPA) of blood samples obtained from patients at baseline and 1 month after immunization. The extension included 405 of the original patients.

Results showed that administration of PPSV23 after PCV13 resulted in GMTs that were noninferior to responses observed after PPSV23 alone for the 12 serotypes common to both vaccines. Moreover, the response was significantly greater for 9 of the 12 serotypes, Dr. Jackson reported. Response to PPSV23 after PCV13 was significantly greater for all 12 serotypes as compared with revaccination with PPSV23 (GMT ratio =2 for all but 1 serotype, which had a ratio of 1.9).

The safety profile associated with revaccination after an initial dose of PCV13 was acceptable, whether revaccination was with PCV13 or PPSV23, Dr. Jackson reported. Revaccination with PPSV23 resulted in more local reactions as compared with PCV13 in patients who initially received either vaccine.

“PCV13 is currently under consideration for approval [in adults] in the US and other countries,” Dr. Jackson and colleagues concluded. “When approved, the results of this study suggest that repeated doses of PCV13, given at an interval of several years, can be used to optimize protection for the lifetime of risk.”

Intervals Between Vaccine Doses

Revaccination at a 1-year interval was the subject of another study reported at IDSA. The trial involved 720 patients ages 60-64 who were randomized to receive 2 doses of PCV13, an initial dose of PCV13 followed by revaccination with PPSV23, or PPSV23 followed a year later by PCV13. The primary outcome was the comparison of GMTs to the 12 common serotypes, reported Dr. Richard N. Greenberg, University of Kentucky, Lexington.

The results were consistent with those reported by Dr. Jackson. PCV13 followed by PPSV23 demonstrated noninferiority to initial vaccination with PPSV23 for all 12 serotypes and superiority for 6 of the 12. PCV13 followed by PPSV23 also demonstrated noninferiority to PPSV23 followed by PCV13 for all 12 serotypes. However, GMTs were significantly greater for 11 of 12 common serotypes when PCV13 preceded PPSV23, as opposed to the reverse order.

“This study showed that PCV13 establishes an immunological memory state that augments the pneumococcal response to subsequent administration of PPSV23 for many of the serotypes common to both vaccines,” explained Dr. Greenberg.“However, when you give PPSV23 first, it results in an immunological memory state that results in a diminished response to subsequent administration of PCV13 for all serotypes.” He added, “The implication is that if you want to revaccinate patients, PCV13 should be given before PPSV23.”

Older Patient Population

Investigators in an international trial examined immunologic response to PCV13 in 98 older patients (mean age 73) who previously had received an initial dose of PCV13, followed by revaccination with PPSV23. The 3 vaccinations were administered at 1-year intervals, according to clinical investigator Dr. Christine Juergens, Berlin, Germany.

The results showed that GMTs were lower for 12 of 13 serotypes after sequential vaccination compared with the response to the first dose of PCV13. GMTs were significantly lower for 10 of the 12.

Adverse events consisted primarily of injection-site reactions, pain and functional limitation in the vaccinated arm. No patient developed serious or unexpected adverse events.

When considered in composite with the study reported by Dr. Jackson, these observations reflect both the potential immunologic benefit of PCV13, and provide support for the negative immunological impact of PPSV23 on subsequent pneumococcal vaccine responses, even over a longer interval between doses, Dr. Juergens and colleagues concluded.

Ongoing Evaluations

During the IDSA scientific sessions, a preliminary clinical evaluation of a 15-valent pneumococcal vaccine demonstrated GMTs comparable to the 7-valent pneumococcal vaccine for the 7 serotypes common to both vaccines, as well as clinically relevant immunologic response to the remaining 8 serotypes contained in the 15-valent vaccine. The study involved 60 healthy adults, a required step before evaluation of the vaccine in children.

Belgian clinical researchers reported significant declines in the incidence of invasive pneumococcal disease (IPD) in infants after introduction of the 7-valent pneumococcal vaccine. Invasive disease caused by the 7 serotypes covered by the vaccine declined by 63% from 2007-2010 (when the vaccine was introduced) and the pre-vaccine period of 2002-2004. Cases caused by the 7 serotypes declined from 69% in the pre-vaccine period to 26% after the vaccine became available (P<0.005).

Introduction of the 7-valent vaccine was credited with eradication of IPD in several age groups in Alberta. Over the course of 13 years, spanning the pre- and post-vaccine periods, the proportion of cases caused by the 7 serotypes covered by the vaccine declined in all age groups, from infants to the oldest patients, Jeanine Leal, MSc, University of Calgary, Alberta, reported during a poster session. Of the 1462 cases identified, investigators found 100% eradication rates in patients 5 months and younger, in ages 5-15 years and in patients 85 and older. Eradication rates were 98% for patients 6-23 months of age, 97% for children ages 2-4 years, 73% for ages 16-64 and 90% for the 65-84 age group.

Summary

Vaccine development has had a major impact on the spread of IPD, and patients of all ages have seemed to benefit. The potential for revaccination and for sequential use of different vaccines has been demonstrated in several studies. The same studies have provided insight into the potential results with various sequential strategies, specifically with respect to varying degrees of immunologic memory states leading to differences in responses to repeat immunizations. New vaccines continue to emerge, suggesting clinicians and their patients may eventually have several immunization options for reducing the spread of pneumococcal disease.