Response to Vyse et al., “A review of current data to support decision making for introduction of next generation higher valency pneumococcal conjugate vaccination of immunocompetent older adults in the UK”

KEYWORDS:

• pneumococcal
• vaccine
• immunogenicity
• immunity
• immunocompetent

Dear Editor:

We read with interest the review by Vyse A et al. to support decision making for introduction of next generation higher valency pneumococcal conjugate vaccination of immunocompetent older adults in the United Kingdom [1]. We would like to address some of the key points that are not in line with the totality of available scientific evidence for the 23-valent pneumococcal polysaccharide vaccine (PPV23) use in immunocompetent adults.

First, the article states that PPV23 provides limited short-term protection against invasive pneumococcal disease [1]. Available evidence demonstrates that PPV23 offers clinical protection for approximately 10–15 years in most healthy adults and may decline with increasing age and time [2]. Such observations are comparable to available data on the duration of protection afforded by PCV13, including results from the CAPiTA study demonstrating declining PCV13 efficacy with age in older adults [3,4]. Of note, analysis of 13 economic evaluations conducted between 2006 and 2018 showed that most of the studies estimated that the effectiveness of PCVs decline to zero after 15–20 years in the CE model, and it also demonstrated that PPV23 effectiveness declines to zero after 5–15 years [4]. Serotype-specific antibody responses have been demonstrated to remain above pre-vaccination levels for up to 9 years following PPV23 administration [5]; furthermore, opsonophagocytic antibody (OPA) responses following PPV23 and PCV13 administration were found to be comparable for up to 5 years [5,6].

Second, the article states that relevant published studies investigating PPV23 protection against pneumonia show considerable variation in study design and clinical outcome targeted, making it difficult to draw definitive conclusions and that there is a lack of consistent evidence demonstrating the effectiveness of PPV23 against Community Acquired Pneumonia (CAP) in older adults [1]. Importantly, due to the lack of serotype-specific diagnostic tests for pneumonia until recently, many historic studies evaluating effectiveness of PPV23 reported on pneumococcal pneumonia caused by any serotype or all cause CAP. Of note, in the CAPiTA trial, efficacy of PCV13 on noninvasive pneumococcal pneumonia by any serotype as well as any CAP was not significant [3,6].

Recent analyses of independent expert committees such as the Advisory Committee on Immunization Practices Working Group (ACIP-WG) and the WHO SAGE Working Group on pneumococcal vaccines as well as peer-reviewed published meta-analyses and systematic reviews, concluded that PPV23 is effective against both invasive and noninvasive pneumococcal disease [^7–10]. Available scientific evidence demonstrates that PPV23 has 73% efficacy against all serotype Invasive Pneumococcal Disease (IPD), up to 77% effectiveness against vaccine-type (VT)-IPD, and 33% effectiveness against VT-Non-bacteremic Pneumococcal Pneumonia (NBPP) in healthy older adults [7,9]. Therefore, it is important to consider PPV23 in the context of a comprehensive pneumococcal disease prevention program.

Third, the authors state that the additional serotypes included in PPV23 not currently in next generation PCVs (i.e. serotypes 2, 9 N, 17 F, and 20) caused only a small proportion of the IPD burden in English and Welsh adults aged ≥65 years [1,11]. Shamez et al. have shown the emergence of certain serotypes, including 9 N at 6.7%, as well as ST 8 at 20% and 12 F at 13%, which are responsible for almost 40% of total invasive pneumococcal disease cases in 2016–2017 [12]. Pneumococcal CAP incidence rates have increased over 5 years particularly in older age groups. PPV23-nonPCV13 serotypes were identified in 431 (40.1%) patients, with serotype 8 being the most common, followed by serotypes 12 F,11A, 22 F, and 9 N [13]. In the United States, the ABC surveillance system showed that there has been a stable increase in both incidence of these unique serotypes in PPV23 not included in next generation PCVs over the last 20 years and the proportion of total IPD cases, which could be due to low vaccination rates in older adults. Thus, there may be further increases in IPD cases due to these STs if PPV23 is not included in recommendations. Additionally, the unique PPV23-nonPCV13 serotypes account for about 1% of hospitalized CAP among older adults. Given an estimated CAP hospitalization incidence of 2093 cases per 100,000 older adults (95% CI, 2000.4–2187.7) and an estimated population of 52 million Americans over the age of 65, PPV23 has the potential to prevent about 2,176 CAP hospitalizations annually due to its unique serotypes based on the PPV23 effectiveness assumption of 20% against NBPP by the ACIP WG [14].

It is important to note that cumulative vaccine coverage rates for PPV23 in adults aged 65 years and over, vaccinated any since 2003 to 31 March 2021 was 70.6% in the UK. However, the proportion of adults aged 65 years only on 31 March 2021 who were vaccinated between 1 April 2020 and 31 March 2021 was 15.1% [15].

Published scientific data are an influential resource for immunization providers and decision makers on immunization committees globally. As such, it is important that publications include a comprehensive review of available evidence in support of claims made in the article. Careful review of these data is important due to the potential global public health implications.

Declaration of interest

R Dawson, U Buchwald, K Johnson, and L Spowart are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, who may own stock and/or hold stock options in Merck & Co., Inc., Kenilworth, NJ, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Acknowledgments

Karyn Davis of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, provided editorial assistance.

Additional information

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.