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PRIORITY PRESS - AMMI Canada - CACMID Annual Conference

Québec City, Quebec/ April 4-6, 2013

Québec City - Prevention of pneumococcal and other vaccine-preventable diseases is challenging in patients with immune deficiency. Vaccines are less immunogenic in this population. Many patients have not had recommended immunizations. New recommendations for the use of the 13-valent conjugate pneumococcal vaccine are based on studies revealing better immunogenicity with conjugate as opposed to polysaccharide formulations. An Ontario centre has designed a unique protocol to ensure that one group of high-risk patients—those starting biologic or other disease-modifying therapies—are fully immunized in the optimal period before their immune status deteriorates.

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

Streptococcus pneumoniae is a potentially deadly source of invasive infection, including sepsis, meningitis and pneumonia. Children, older adults and individuals with illnesses or undergoing treatment leading to immune compromise are most vulnerable. Several vaccines are now available to help prevent invasive pneumococcal disease (IPD).

Aging and Immunosuppression

Numerous studies confirm the elevated incidence of pneumococcal disease in patients with immunosuppressive conditions, indicated Dr. Deepali Kumar, Associate Professor, University of Alberta, Edmonton, and a member of the National Advisory Committee on Immunization (NACI). Immunodeficiency is more common than is widely perceived, she noted. In addition to such clear-cut causes as human immunodeficiency virus (HIV) infection, solid organ and hematopoietic stem cell transplantation (HSCT), malignancy and chemotherapy and biologic therapies for inflammatory diseases, immunodeficiency is a natural result of aging as well as diabetes, lung, renal or liver disease.

Pneumococcal and other vaccines are less immunogenic in this high-risk population than in healthier individuals, Dr. Kumar explained. “With age, the thymus involutes, so fewer naive T-cells are produced. Defects in B-cell isotype switching result in [poor quality] antibodies...The T-cell repertoire, which is generally diverse and able to respond to a large variety of antigens, becomes restricted. With immunosuppression, similar things happen. It’s almost like accelerated aging [and] if we put patients on immunosuppression there is decreased T-cell proliferation in response to antigen [and] decreased antibody production by B cells.”

Immunologic Response to Conjugate Vaccine

New recommendations from NACI suggest that in high-risk patients aged ≥18 years, vaccination with the 13 valent conjugate pneumoccocal vaccine (PCV-13) may improve protection against IPD. Although there is a dearth of efficacy and effectiveness data in this area, immunologic response data on these regimens are promising, stated Dr. Caroline Quach, Associate Professor of Pediatrics, Co-director of the McGill University Health Centre Vaccine Study Centre, Montreal, Quebec, and a NACI member.

A potential explanation for a superior response to a conjugate vaccine is that its mechanism of action involves T-cell activation, while polysaccharide vaccines are T-cell-independent, Dr. Kumar told delegates. With a conjugate vaccine, “the activated T cells stimulate the B cells to produce antibodies… In both types of vaccine, the B-cell is producing antibodies but in the conjugated form the B-cell is producing better antibodies, what we call more ‘high affinity’ or ‘high avidity’ antibodies. The other thing that happens is that memory B cells are being produced. And it’s important for memory to be produced because we require memory for the eventual boost of antibodies.”

Transplant Patients

Patients undergoing HSCT are about 30 times more likely than those in the general population to develop IPD. The risk is highest in the first year after the procedure. Polysaccharide vaccination is not highly immunogenic in this group. NACI now recommends PCV-13. Based on available evidence, notably a study comparing early and late immunization, “we recommend that a primary series of 3 doses be started between 3 and 9 months [post-transplant]. The doses should be administered at least 4 weeks apart, and followed by a booster dose of pneumococcal polysaccharide vaccine 6 to 12 months after the last conjugate vaccine dose,” explained Dr. Quach.

IPD is also far more likely (relative risk 25) in patients who undergo solid-organ transplantation (especially lung or liver). Although the data for PCV-13 in this patient group is less compelling, a study of S. pneumoniae antibody titers in 60 kidney transplant recipients determined that at 8 weeks, the response to PCV-13 was better than that to PPV-23. “It was significantly greater for a couple of the serotypes [and for others there was a positive trend]. The patients who responded to 6 or 7 serotypes had all received conjugated vaccine,” Dr. Kumar stated. These benefits were not sustained out to 3 years, she acknowledged. At this point, the titers had declined regardless of vaccine given. A prime-and-boost strategy using PCV-13 and then PPV-23 may be useful because “the conjugate gives better initial titers and the polysaccharide…expands the coverage to other serotypes.” Further investigation of this strategy—for example, with different intervals between vaccines—may be appropriate, she suggested.

HIV-Positive and Other High-Risk Patients

NACI indicates that HIV-positive patients already vaccinated with PPV-23 should receive a dose of PCV-13 at least 1 year later. Vaccine-naive patients should start with 1 dose of PCV-13, followed by a dose of PPV-23 8 weeks later. One lifetime booster dose of PPV-23 is recommended; it should be administered at least 8 weeks after PCV-13 and at least 5 years after any previous PPV-23 dose. These recommendations are based on studies demonstrating a better initial immune response with a conjugate vaccine and a better booster response with the polysaccharide, Dr. Quach explained. There is currently no evidence that a booster dose with PCV-13 confers additional benefit.

Table 1.

For generally healthy elderly patients, “We are continuing to recommend the 23 valent vaccine,” Dr. Quach affirmed. The results of the CAPITA study, which will determine the incidence of community-acquired pneumonia in patients given PCV-13 or placebo, may offer information to help NACI reassess recommendations for this population.

PCV-13 may be administered to adults with other immunocompromising illnesses or undergoing immunosuppressive therapy (Table 1). As with the HIV population, in patients already vaccinated with PPV-23, a dose of conjugate vaccine should be given at least 1 year after the PPV-23 dose. In vaccine-naive patients, pneumococcal vaccination should be started with PCV-13, followed by PPV-23 8 weeks later. Again, one lifetime booster dose of PPV-23 is recommended, to be administered at least 8 weeks after PCV-13 and no sooner than 5 years after any previous PPV-23 dose.

Timing of Vaccination

Clinicians can improve their patients’ protection against IPD and other infections by ensuring those at risk are vaccinated before their immune status is altered. For solid-organ transplant candidates, “the best time to immunize is before transplant, which is when all vaccines work a lot better,” remarked Dr. Kumar. Similarly, when a patient is taking high-dose steroids, is destined to undergo chemotherapy or has an inflammatory disease course suggesting an eventual need for biologic therapy, it is appropriate to review and correct their immunization status early on, stated Carolyn Whiskin, pharmacist, Consultant, Charlton Centre for Specialized Treatments, Hamilton, Ontario. In her experience, few health care institutions or physicians have a protocol to ensure vaccination of immunocompromised patients. The majority of patients coming to her centre for biologic therapies do not have their vaccinations up to date. Importantly, if an infection occurs while the patient is on disease-modifying therapy, the impact goes beyond that of the infection itself. Any consequent interruption or delay in administration of the therapy can have a significant impact on the patient’s symptoms, disease course and quality of life.

To help address this care gap, Ms. Whiskin and her colleagues developed a unique vaccine protocol for their centre. aimed at summarizing guidelines and ensuring communication between practitioners on the patient’s care team so that one of them orders and/or administers all relevant vaccinations during the window of opportunity before immunosuppressive therapy begins. “I believe the key to these [immunization] guidelines is implementation. We need more checkpoints in the system,” Ms. Whiskin remarked. So far, the response among referring physicians is very positive.