Thank you for your interest in CCO content. As a guest, please complete the following information fields. These data help ensure our continued delivery of impactful education.
Become a member (or login)? Member benefits include accreditation certificates, downloadable slides, and decision support tools.
Sherrilyn and Ken Fisher Professor of Medicine
Division of Infectious Diseases
Johns Hopkins University School of Medicine
Paul Auwaerter, MD, MBA, has disclosed that he has received consulting fees from Adaptive Biotherapeutics, EMD Serono, and Pfizer and funds for research support from Humanigen, MicroB-Plex, and Pfizer.
Provided that the Advisory Committee on Immunization Practices (ACIP) addressed novel pneumococcal immunizations in October 2021, I’d like to share my thoughts on several relevant studies presented at IDWeek 2021 that were particularly interesting. These studies include examinations of a new pneumococcal disease vaccination strategy in adults, healthcare professional preferences with regard to ACIP pneumococcal vaccination recommendations, and the results of 2 phase III trials with the 15-valent pneumococcal conjugate vaccine (V114) in children.
V114 in Adults
The PNEU-DAY study showed that the 15-valent conjugate vaccine V114 (recently approved by the FDA in adults), followed 6 months later by the polysaccharide 23-valent vaccine (PPSV23), was immunogenic and well tolerated in participants 18-49 years of age. V114 contains 2 additional serotypes, 22F and 33F, that are not included in the 13-valent conjugate vaccine. Of note, serotypes 3, 22F, and 33F are associated with an increasing and substantial number of cases of invasive pneumococcal disease. I think that the PNEU-DAY study shows these vaccines perform as hoped, eliciting antibody responses in adults. However, there are no randomized controlled studies of the clinical efficacy or outcomes of V114. As usual with many vaccine studies, the comparison is with earlier vaccines, and the study depends on observed surrogate serologic responses.
V114 in Infants and Children
Currently, V114 is approved in adults only, not in children who remain with the current recommendation to receive the PCV13 vaccine. The results of 2 phase III clinical trials with V114 in infants and children were also presented at IDWeek 2021. In the PNEU-DIRECTION trial, Bili and colleagues showed that V114 alone and in mixed-dose regimens with PCV13 was safe and generated similar immune responses in infants. In the PNEU-PLAN trial, Banniettis and colleagues found that V114 and PCV13 given as a “catch-up vaccination” was well tolerated, safe, and immunogenic in pneumococcal vaccine–naive children aged 7 months to 17 years. These 2 trials show that the V114 vaccine performs well in these pediatric age groups, including the additional 22F and 33F serotype responses.
Pneumococcal Vaccination Recommendations
I find that many of my colleagues are unaware of why the ACIP has changed pneumococcal vaccine recommendations over recent years. For example, what is the basis for these changes, or why there is now an additional updated recommendation? We do not see pneumococcal disease or invasive disease as frequently as we have in the past, possibly because people smoke less and efforts have been made to immunize children against pneumococci. The thought process of some healthcare professionals may be that 2 vaccines have to be better than one. However, cost-effectiveness studies found that using conjugate vaccines in adults to provide a quality-adjusted life-year can cost more than $500,000. I think the cost also influences vaccine decision makers about whether to adopt or embrace additional vaccine recommendations for conjugate vaccines in adults on a widespread basis.
The study by Vietri and colleagues showed that among primary care providers, including physicians, physician assistants, nurse practitioners, and pharmacists, there was a strong preference for simplification of pneumococcal immunization recommendations. This is important because the 2019 pneumococcal vaccine schedule is complex. For example, if a patient is 65 years of age or older and has not received a pneumococcal vaccine, he or she can get the PPSV23 vaccine or get the PCV13 followed by PPSV23 with shared decision-making. Healthcare professionals need to understand vaccine recommendations so that they can be both easily implemented and discussed with patients. When shared decision-making is executed instead of a strong recommendation, providers can optimize opportunities to discuss the advantages and disadvantages of indicated vaccines with their patients.
Putting It in Context
I practice both internal medicine and infectious diseases consultation. I have noticed that the pneumococcal disease incidence has decreased compared with my experience 20 and 30 years ago. Reasons for this are likely manifold. First, the pneumococcal polysaccharide vaccine is efficacious in preventing invasive pneumococcal disease (but not as robustly known for pneumonia). Second, studies during the past decade have shown that the widespread adoption of pneumococcal immunizations in children has indirectly decreased pneumococcal disease rates in adults. Children appear to be one of the leading carriers of Streptococcus pneumoniae. Of note, the CAPITA study demonstrated that PCV13 protected against invasive pneumococcal disease caused by vaccine serotypes contained in the vaccine.
Thanks to the widespread adoption of pneumococcal immunizations in children and the results of the randomized, double-blind, placebo-controlled CAPITA study, the conjugate vaccine followed by PPSV23 was recommended for adults aged 65 years and older in 2014. This was modified in 2019 to the shared decision-making recommendation, since there was a less obvious need to use both vaccines. The basis for the shared-decision model resting on the sharp decline of pneumococcal disease in adults became apparent, and there appeared to be minimal impact on pneumococcal disease in adults since PCV13 was recommended in 2014.
The V114 vaccine adds two new serotypes and provides a more robust response to serotype 3, which is also present in PCV13 and PPSV23. I think adding more serotypes is helpful, as an increased prevalence of nonvaccine-covered serotypes has been observed. However, how it will be handled in conjunction with the pneumococcal polysaccharide vaccine is uncertain in my mind, and we will wait for the ACIP’s decision. So far, the ACIP’s proposed policy options from an October 20, 2021, meeting include recommendations for adults based on the newly approved 20-valent conjugate vaccine alone or a 15-valent conjugate vaccine plus PPSV23, depending on age and risk factors. It will be interesting to learn how providers plan to implement any updated ACIP recommendations in clinical practice.
Best Practices for Implementing New ACIP Recommendations
I follow the ACIP recommendations closely, but given the frequency of changes, it can be confusing to frame decisions regarding pneumococcal immunizations in adults. I like to have best practice alerts in our electronic medical records that remind me to consider whether my primary care patients benefit from a vaccine. I also want to familiarize myself with the recommendations and the evidence to explain the immunization strategy to patients. I find that a strong recommendation from me is influential in convincing hesitant patients to get vaccinated. This is especially true for people with risk factors such as a history of recurrent pneumonia, smoking, asthma, and other comorbidities.
In my practice, I am particularly interested in using new vaccines that offer broader coverage of serotypes for people who have cochlear implants, have had a splenectomy, have advanced COPD, or are active smokers. Study results influence me, and I think these vaccines do the job serologically as assessed in vitro. Although there may be some additional benefit in using the new vaccines, only time will tell if changes in the constitution of pneumococcal vaccines will affect infection rates.
How do you counsel your patients about their risks of invasive pneumococcal disease and vaccine recommendations? Answer the polling question and join the conversation by posting in the discussion section.