March 12, 2020
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Prime-boost vaccination enhances immunogenicity in patients with rheumatic disease

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Patients with inflammatory rheumatic disease receiving conventional DMARDs and a prime-boost vaccination strategy — a dose of pneumococcal conjugate vaccine and a dose of 23-valent polysaccharide vaccine — saw improved immunogenicity, compared with single pneumococcal conjugate vaccination, according to data published in Arthritis Research & Therapy.

“Since 2012, the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommendations for adults with immunocompromising conditions is to receive immunization with a dose of PCV13, followed after at least 8weeks by a dose of PPV23, because of the wider serotype coverage,” Per Nived, MD, of the Central Hospital Kristianstad, in Sweden, and colleagues wrote.

“The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Vaccine Study Group (EVASG) also recommends that at-risk adults receive this vaccine schedule, which we refer to as the prime-boost pneumococcal vaccination strategy,” they added. “Whether the prime-boost strategy has advantages over single-dose PCV13 or PPV23 in patients with inflammatory rheumatic diseases, and in the context of different immunosuppressive treatments are still not fully understood.”

Nived and colleagues sought to determine whether a prime-boost strategy enhances antibody response, compared with a single PCV dose, among patients with inflammatory rheumatic diseases who receive various immunosuppressive drugs. They recruited and studied 30 patients treated with rituximab (Rituxan, Genentech), 23 receiving abatacept (Orencia, Bristol-Myers Squibb), 27 on monotherapy with conventional DMARDs — methotrexate, azathioprine or mycophenolate mofetil — and 28 control participants from Skåne University Hospital in Lund and the Central Hospital in Kristianstad.

Image of vaccine 
Patients with inflammatory rheumatic disease receiving conventional DMARDs and a prime-boost vaccination strategy saw improved immunogenicity, compared with single pneumococcal conjugate vaccination, according to data .
Source: Adobe

All participants received immunizations with a PCV dose followed by PPV23 after 8 weeks or more. The researchers used a multiplex microsphere immunoassay in blood samples prior to and at 4 to 8weeks after each vaccination to determine specific antibodies to 12 serotypes included in both vaccines. They defined a positive antibody response as a twofold or greater increase in serotype-specific IgG concentration following vaccination. Putative protective level was defined as an IgG of 1.3 g/mL or greater. Investigators compared the number of serotypes meeting both standards across all treatment groups.

According to the researchers, prime-boost vaccination increased the number of serotypes with positive antibody response in patients treated with abatacept (P=.02), conventional DMARDs (P=.01) and controls (P=.01), compared with the single-dose PCV. However, they did not see this effect in those treated with rituximab. After PCV-plus-PPV23 immunization, the number of serotypes with positive antibody response was significantly lower in all treatment groups compared with controls, but was lowest in the rituximab group, followed by the abatacept and conventional DMARD groups (P<.001).

Additionally, the number of serotypes with putative protective levels after PCV-plus-PPV23 increased significantly only in patients treated with conventional DMARDs (P=.03) and the control group (P=.001), compared with PCV alone. In the multivariate linear regression model, rituximab was associated with large reduction in the number of serotypes with positive antibody response to PCV-plus-PPV23 (P<.001). This was also demonstrated in patients treated with abatacept (P=.005) or conventional DMARDs (P<.001).

Opsonophagocytic activity was reduced in the rituximab (P<.001), abatacept (P=.02) and conventional DMARD (P=.02) groups, compared with controls.

“Prime-boost vaccination strategy might be more beneficial compared to a single vaccine dose in patients treated with conventional DMARDs and also in patients receiving abatacept,” Nived and colleagues wrote. “Rituximab treatment lead to a large reduction in immunogenicity of single-dose pneumococcal conjugate vaccine, and a subsequent PPV23 dose did not improve antibody response. Pneumococcal vaccination should be strongly encouraged before starting rituximab.” – by Jason Laday

Disclosures: The researchers report no relevant financial disclosures.