PCV13 Vaccination of Adults against Pneumococcal Disease: What We Have Learned from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA)

The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA) evaluated older adult pneumococcal vaccination and was one of the largest vaccine clinical trials ever conducted. Among older adults aged ≥65 years, the trial established 13-valent pneumococcal conjugate vaccine (PCV13) efficacy in preventing first episodes of bacteremic and nonbacteremic pneumococcal vaccine serotype (VT) community acquired pneumonia (CAP), and of vaccine serotype invasive pneumococcal disease (VT-IPD). Since the publication of the original trial results, 15 additional publications have extended the analyses. In this review, we summarize and integrate the full body of evidence generated by these studies, contextualize the results in light of their public health relevance, and discuss their implications for the assessment of current and future adult pneumococcal vaccination. This accumulating evidence has helped to better understand PCV13 efficacy, serotype-specific efficacy, efficacy in subgroups, the interpretation of immunogenicity data, and the public health value of adult PCV vaccination.

Epidemiology of Streptococcus pneumoniae serotypes in children before and after pneumococcal vaccination

Aim. To investigate how the pneumococcal vaccination affects the distribution of Streptococcus pneumoniae serotypes.Materials and Methods. In 2011-2019, 1,852 healthy children (1,354 aged ≤ 5 years and 480 aged from 6 to 17 years) were examined for the nasopharyngeal pneumococcal carriage. Of them, 539 children were tested before the start of pneumococcal vaccination (2011-2014), while 1,313 were tested during the vaccine campaign (2015-2019). Pneumococcal strains were serotyped using multiplex polymerase chain reaction.Results. Streptococcus pneumoniae serotype distribution considerably differed between children ≤ 5 and 6-17 years of age. Serotypes 23F, 19F, 19A, 6AB, and 15BC were prevalent in children ≤ 5 years of age while the older children were characterised by a high prevalence of capsular serotypes (3 and 33AF/37), serogroup 9 (9AV and 9LN), non-typeable streptococci, as well as 19F, 6AB and 6CD serotypes. Vaccination was associated with a significantly decreased prevalence of Streptococcus pneumoniae carriage (from 41.5% to 19.2%) among children ≤ 5 years of age, while this reduction was less pronounced (from 13.5 to 9.0%) in older children. Vaccination led to the shift in the distribution of pneumococcal serotypes towards an increased prevalence of non-vaccine serotypes that was particularly prominent in children ≤ 5 years of age. In particular, vaccination reduced the prevalence of 23F and 19A pneumococcal serotypes but heightened prevalence of 11AD serotype and to the appearance of previously undetected serotypes such as 8, 10A, 17F, 22F, 24ABF, 34, and 39.Conclusion. Pneumococcal vaccination decreased prevalence of pneumococcal carriage, yet causing a serotype replacement effect requiring improved microbiological monitoring in children of all age groups.

The Health Professional’s View on the Inclusion of Age in the Recommendations for Pneumococcal Vaccination: Results of a Cross-Sectional Survey in France

Elderly people are at high risk for pneumococcal infections. However, older age is not an eligibility factor for pneumococcal vaccination in France. Adults with certain co-morbidities or immunocompromised states are eligible for vaccination, which leaves adults aged ≥65 years without comorbidities at-risk for pneumococcal infections. The objective of the study was to evaluate the acceptability to healthcare professionals (HCPs) of extending pneumococcal vaccination to all individuals ≥65 years. Based on themes identified in semi-structured interviews with 24 HCPs, a representative sample of 500 general practitioners and pharmacists were surveyed about their knowledge, attitudes and beliefs with respect to pneumococcal vaccination for individuals ≥65 years. Current recommendations for pneumococcal vaccination are poorly understood by participants (mean score: 5.8/10). Respondents were generally supportive of inclusion of age in vaccination recommendations (7.5/10), with 58% being very supportive. For 72% of HCPs, this would contribute to improved vaccination coverage. The strategy could be facilitated by associating pneumococcal vaccination with the influenza vaccination campaign (8.3/10). Pharmacists were favourable to participating in pneumococcal vaccination (8.5/10). In conclusion, extension of pneumococcal vaccination to all people aged ≥65 years would be welcomed by HCPs, simplifying identification of patients to be vaccinated and potentially improving vaccination coverage.

Promising Expectations for Pneumococcal Vaccination during COVID-19

The emergence of new viral infections has increased over the decades. The novel virus is one such pathogen liable for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, popularly known as coronavirus disease 2019 (COVID-19). Most fatalities during the past century’s influenza pandemics have cooperated with bacterial co/secondary infections. Unfortunately, many reports have claimed that bacterial co-infection is also predominant in COVID-19 patients (COVID-19 associated co/secondary infection prevalence is up to 45.0%). In the COVID-19 pandemic, Streptococcus pneumoniae is the most common coinfecting pathogen. Half of the COVID-19 mortality cases showed co-infection, and pneumonia-related COVID-19 mortality in patients >65 years was 23%. The weakening of immune function caused by COVID-19 remains a high-risk factor for pneumococcal disease. Pneumococcal disease and COVID-19 also have similar risk factors. For example, underlying medical conditions on COVID-19 and pneumococcal diseases increase the risk for severe illness at any age; COVID-19 is now considered a primary risk factor for pneumococcal pneumonia and invasive pneumococcal disease. Thus, pneumococcal vaccination during the COVID-19 pandemic has become more critical than ever. This review presents positive studies of pneumococcal vaccination in patients with COVID-19 and other medical conditions and the correlational effects of pneumococcal disease with COVID-19 to prevent morbidity and mortality from co/secondary infections and superinfections. It also reports the importance and role of pneumococcal vaccination during the current COVID-19 pandemic era to strengthen the global health system.

Establishment of an ELISpot Assay to Detect Cellular Immunity against S. pneumoniae in Vaccinated Kidney Transplant Recipients

In organ transplant recipients, the rate of invasive pneumococcal diseases is 25 times greater than in the general population. Vaccination against S. pneumoniae is recommended in this cohort because it reduces the incidence of this severe form of pneumococcal infection. Previous studies indicate that transplant recipients can produce specific antibodies after pneumococcal vaccination. However, it remains unclear if vaccination also induces specific cellular immunity. In the current study on 38 kidney transplant recipients, we established an interferon-γ ELISpot assay that can detect serotype-specific cellular responses against S. pneumoniae. The results indicate that sequential vaccination with the conjugated vaccine Prevenar 13 and the polysaccharide vaccine Pneumovax 23 led to an increase of serotype-specific cellular immunity. We observed the strongest responses against the serotypes 9N and 14, which are both components of Pneumovax 23. Cellular responses against S. pneumoniae correlated positively with specific IgG antibodies (r = 0.32, p = 0.12). In conclusion, this is the first report indicating that kidney transplant recipients can mount specific cellular responses after pneumococcal vaccination. The ELISpot we established will allow for further investigations. These could help to define, for example, factors influencing specific cellular immunity in immunocompromised cohorts or the duration of cellular immunity after vaccination.

Vaccine Responses in Adult Hematopoietic Stem Cell Transplant Recipients: A Comprehensive Review

Consensus on timing of post-hematopoietic stem cell transplantation (HSCT) vaccination is currently lacking and is therefore assessed in this review. PubMed was searched systematically for articles concerning vaccination post-HSCT and included a basis in predefined criteria. To enable comparison, data were extracted and tables were constructed per vaccine, displaying vaccine response as either seroprotection or seroconversion for allogeneic HSCT (alloHSCT) and autologous HSCT (autoHSCT) separately. A total of 33 studies were included with 1914 patients in total: 1654 alloHSCT recipients and 260 autoHSCT recipients. In alloHSCT recipients, influenza vaccine at 7–48 months post-transplant resulted in responses of 10–97%. After 12 months post-transplant, responses were >45%. Pneumococcal vaccination 3–25 months post-transplant resulted in responses of 43–99%, with the response increasing with time. Diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenzae type b at 6–17 months post-transplant: 26–100%. Meningococcal vaccination at 12 months post-transplant: 65%. Hepatitis B vaccine at 6–23 months post-transplant: 40–94%. Measles, mumps and rubella at 41–69 months post-transplant: 19–72%. In general, autoHSCT recipients obtained slightly higher responses compared with alloHSCT recipients. Conclusively, responses to childhood immunization vaccines post-HSCT are poor in comparison with healthy individuals. Therefore, evaluation of response might be indicated. Timing of revaccination is essential for optimal response. An individualized approach might be necessary for optimizing vaccine responses.