Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine Against Pneumococcal Diseases Among the Elderly Aged 60 Years or Older: A Matched Test Negative Case-Control Study in Shanghai, China

Background:Streptococcus pneumoniae infection among adults, especially in adults over 60 years old in China results in a large number of hospitalizations and a substantial financial burden. This study assessed the vaccine effectiveness (VE) of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases among the elderly aged 60 years or older in Shanghai, China.Methods: We conducted a test-negative case–control study among the elderly aged 60 years or older who sought care at hospitals in 13 districts of Shanghai from September 14, 2013 to August 31, 2019. A case was defined as pneumococcal disease and testing positive for Streptococcus pneumoniae. Controls had symptoms congruent with pneumococcal disease but were negative for Streptococcus pneumoniae. We conducted 1:2 matching by gender, age, hospital and admission date. Vaccination status was verified from the immunization system database. VE was calculated with conditional logistic regression according to the formula (1–OR) ×100%.Results: Overall, 603 adults aged 60 years or older with pneumococcal disease and positive for Streptococcus pneumoniae were included as cases, and 19.6% (118 persons) had a recorded PPV23 vaccination. The controls included 1,206 adults, whose vaccination rate was 23.8% (287 persons). The VE against pneumococcal diseases among the whole population was 24% (95% CI: 2%, 40%) and among women 44% (95% CI: 6%, 67%). After adjusting for multiple variables, the effectiveness of PPV23 against pneumococcal diseases was still statistically significant with VE for all of 25% (95% CI: 3%, 42%) and VE for women of 49% (95% CI: 11%, 71%).Conclusion: PPV23 was effective against pneumococcal diseases in adults aged 60 years or older in Shanghai, China. Its relatively high effectiveness among women warrants this group to be particularly targeted for vaccination, with further research on why vaccination effectiveness is less among men.

Persistence of Antibody After a Vi-Tetanus Toxoid Conjugate Vaccine and Effect of Boosting With a Plain Polysaccharide Vaccine on Vi Antibody and Antigen-Specific B Cells

BackgroundSalmonella enterica serovar Typhi is estimated to cause 9 to 13 million cases of typhoid fever annually. Typhoid conjugate vaccines represent a promising prophylactic measure to prevent disease, but there are few data assessing persistence of immunity. The effect of a Vi polysaccharide booster vaccine in individuals previously vaccinated with the Vi-tetanus toxoid typhoid conjugate vaccine has not been assessed previously.MethodsThirty five healthy adult volunteers received a single dose of the Vi conjugate vaccine (Vi-TT) and 37 received a single dose of Vi polysaccharide vaccine (Vi-PS) prior to oral challenge with live S. Typhi bacteria as part of a randomised controlled, phase 2b study. In addition to data previously published showing persistence of Vi IgG and IgA antibodies for 7 months after Vi vaccination, titres were measured at intervals until 13 months post-vaccination. Ten participants who received Vi-TT (both challenged and unchallenged) were re-vaccinated with Vi-PS at an interval of 19-23 months post-prime. Anti-Vi IgG and IgA titres, and Vi-specific antibody secreting cells and memory B cells were measured at seven days and one month post-boost.FindingsVi IgG and IgA antibody titres remained significantly elevated above baseline levels 13 months after priming with Vi-TT, with a 4-fold rise retained in 90% and 88% of recipients (Vi IgG and IgA, respectively). Anti-Vi IgG and IgA antibody titres were found to persist at higher levels in participants who received a single dose of Vi-TT than in those who received Vi-PS. No significant boost in Vi-antibody titre was observed in response to oral challenge with S. Typhi bacteria, one month after vaccination. Following a Vi-PS booster vaccination in those previously vaccinated with Vi-TT, anti-Vi IgG and IgA titres were significantly elevated, with similar titres observed at one month post-boost compared with one month after primary vaccination. The frequency of Vi-specific IgA antibody secreting cells increased significantly 7 days post-boost compared with pre-boost. No memory B cell response was observed following Vi-PS booster vaccination.InterpretationStrong persistence of anti-Vi IgG and IgA following Vi-TT vaccination suggests that the conjugate vaccine may offer durable protection, supporting its use in endemic settings.

Immunogenicity, safety and efficacy of 23-valent pneumococcal polysaccharide vaccine in patients with inflammatory joint diseases (preliminary data)

Intoduction. Currently, for the treatment of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA), basic anti-inflammatory drugs and biological drugs are widely used to effectively control the activity of the disease. However, the use of these drugs is associated with an increased risk of developing comorbid infections, some of which can be prevented by vaccination. Objective. To evaluate the immunogenicity, safety, and clinical efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV-23) in patients with RA and SpA.Materials and methods. The study included 122 patients: 79 - with RA, 43-with SpA. Most patients had a history of two or more cases of lower respiratory tract infections, 2 patients reported a monthly exacerbation of chronic sinusitis, one patient reported the development of otitis media every 2-3 months. At the time of inclusion in the study, most patients received immunosuppressive therapy. PPV-23 was administered in an amount of 1 dose (0.5 ml) subcutaneously against the background of anti-rheumatic therapy. The level of antibodies to pneumococcal capsular polysaccharide was determined using the EIA PCP IgG kit (TestLine Clin-ical Diagnostics s.r.o., Czech Republic) before vaccination, 1, 3 and 12 months after vaccination. In addition, the tolerance of PPV-23, the frequency of pneumonia, and the effect on the activity of RA and SpA were evaluated (according to the dynamics of DAS28 and BASDAI).Results. At 1, 3, and 12 months after vaccination, the concentration of antibodies to pneumococcal capsular polysaccharide was significantly higher than the baseline values, which indicates sufficient immunogenicity of PPV-23. There was no negative effect of vaccination on the activity of the underlying disease and the occurrence of new autoimmune disorders. In the majority of patients (67% - RA, 81.4% - SpA), the tolerance of the vaccine was good. During the follow-up period, none of the patients developed pneumonia. Patients suffering from frequent sinusitis and otitis media reported the absence of these infections after vaccination.Conclusion. Preliminary results of the study indicate sufficient immunogenicity, safety, and clinical efficacy of PPV-23 in patients with RA and SpA.

Cost-Effectiveness Analysis of 23-Valent Pneumococcal Polysaccharide Vaccine Program for the Elderly Aged 60 Years or Older in Shanghai, China

Background: The pneumococcal vaccine has been considered as the most effective measure to prevent pneumococcal diseases. In 2013, Shanghai launched a major public health program to vaccinate people aged 60 years or older with 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV-23) free of charge. By the end of June 2020, a total of 1.56 million old people had been vaccinated free of charge.Objective: To evaluate the cost-effectiveness of PPSV-23 vaccination program in Shanghai from the health system perspective.Methods: According to the actual number of people aged 60 years or older with PPSV-23 vaccination in Shanghai from 2013 to 2018, a multi-cohort Markov model for life-time was developed to compare health and economic outcomes of vaccinated people vs. if they were not vaccinated for PPSV-23. Cost effectiveness was reported as incremental cost effectiveness ratio (ICER). A 5% discount rate was used for both costs and health outcomes. In addition, one-way sensitivity analysis was used to test the model's robustness.Results: By the end of 2018, a total of 1,091,967 people aged 60 years or older were vaccinated with PPSV-23 in Shanghai, China. Comparing with the unvaccinated circumstances, PPSV-23 vaccination would cost US $19.62 million more and receive an additional 10,321.3 quality-adjusted life-year (QALY). PPSV-23 was associated with the ICER of $190.1 per QALY gained. The Results were sensitive to the variation of vaccine effectiveness against community-acquired pneumonia (CAP), and disease incidence, mortality, and costs of CAP. In all sensitivity analysis, the PPSV-23 was economical.Conclusion: The PPSV-23 vaccination program in Shanghai was cost-effective. With the further development of the project, the administrative costs of the vaccine will be reduced, making it more cost-effective.

POS1151 IMMUNOGENICITY AND SAFETY OF 23-VALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE IN PATIENTS WITH SPONDYLOARTHRITIS.

Background:Currently, for the treatment of patients with spondyloarthritis (SpA), basic anti-inflammatory drugs and biological drugs are widely used to effectively control the activity of the disease. At the same time, the use of these drugs is associated with an increased risk of developing infections, some of which can be prevented by vaccination.Objectives:The aim of the study was to evaluate the immunogenicity and safety of the 23-valent pneumococcal polysaccharide vaccine (PPV-23) in patients with SpA.Methods:The study included 42 patients with SpA: 30 men, 12 women, age 22-60 years, disease duration 14.8±10.6 years. Ankylosing spondylitis was diagnosed in 30 patients, psoriatic spondyloarthritis – in 12 patients. Activity of diseases was assessed as high in 78% of patients (median BASDAI index was 5.3 [4.1; 6.8]). At the time of inclusion in the study, all patients received nonsteroidal anti-inflammatory drugs, 14 patients - methotrexate, 10 - sulfasalazine, 6 - glucocorticoids, 2 - leflunomide, 2 - etanercept, 2 - secukinumab. 15 patients were planned to be prescribed secukinumab, 3 – etanercept, 3 - adalimumab, 1 – golimumab. 7 patients had a history of more than 2 cases of lower respiratory tract infections, 2 patients reported a monthly exacerbation of chronic sinusitis, 1 patient – the development of otitis every 2-3 months, requiring the use of antibacterial drugs. PPV-23 was administered in the amount of 1 dose (0.5 ml) subcutaneously into the deltoid muscle against the background of anti-rheumatic therapy. The level of antibodies to pneumococcal capsular polysaccharide was determined using the EIA PCP IgG kit (TestLine Clinical Diagnostics s.r.o., Czech Republic) before vaccination, 1, 3 and 12 months after vaccination.Results:The dynamics of the concentration of antibodies to pneumococcal capsular polysaccharide in patients with SpA is presented in the Table 1.Table 1.Concentration of pneumococcal antibodies, U/ml, Me [25; 75 percentile]1 visit (initial)2 visit (after 1 month)3 visit (after 3 month)4 visit (after 12 month)80.0 [35.2; 154.0]160.1 [73.5; 245.7] *214.5 [103.2; 255.0] **175.0 [120.1; 260.1] **p=0.01 **p=0.005At 1, 3 and 12 months after vaccination, the concentration of antibodies to pneumococcal capsule polysaccharide was significantly higher compared to the baseline values. In 81% of patients, vaccination tolerance was good. Reactions at the injection site (pain, swelling and hyperemia of the skin up to 2 cm in diameter), resolved independently after 1-5 days, were observed in 6 patients. In 2 patients, a severe local reaction was registered in the form of pain in the arm, infiltration and hyperemia of the skin up to 8 and 15 cm in diameter, respectively, accompanied by low-grade fever in one patient for 2 days, and febrile fever in the other for 3 days. In both cases, these symptoms were completely stopped after administration of paracetamol and antihistamines. Exacerbation of SpA and the emergence of new autoimmune disorders were not detected. During the follow-up period, no patients developed lower respiratory tract infections. Patients suffering from frequent sinusitis and otitis reported the absence of these infections after vaccination.Conclusion:The obtained data indicate satisfactory immunogenicity and good tolerability of PPV-23 in patients with SpA. Further studies are needed to better assess the immunogenicity and safety of vaccine, as well as to study of the influence of anti-rheumatic therapy on the effectiveness of immunization.Disclosure of Interests:None declared.

Invasive Pneumococcal Disease in Adults in Portugal: The Importance of Serotypes 8 and 3 (2015–2018)

Increasing the uptake of the 13-valent pneumococcal conjugate vaccine (PCV13) in children is expected to alter the serotypes causing invasive pneumococcal disease (IPD) in adults due to herd protection. We characterized 2172 cases of adult IPD in 2015–2018 in Portugal after the introduction of PCV13 in the national immunization plan of 2015. Among the 58 detected serotypes, serotypes 8 (n = 413; 19%), 3 (n = 334; 15%), 22F (n = 148; 7%), 14 (n = 138; 6%), and 19A (n = 116; 5%) were the most frequent. Among PCV13 serotypes, 7F and 19A IPD decreased, but serotype 3 IPD remained stable. The non-PCV13 serotypes were a heterogeneous group, with serotypes 23A and 23B enriched among CSF cases; serotype 8 associated with younger patients; and serotypes 22F, 6C, and 31 associated with older patients. The continued increase of serotype 8 IPD was one of the drivers for the increased coverage of the 23-valent pneumococcal polysaccharide vaccine (PPV23; 80% in 2015–2018). Antimicrobial resistance was associated with older age and serotypes 6C, 11A, 14, 15A, 19A, and 19F. Three years after the introduction of PCV13 in the NIP with an uptake of >95%, the proportion of PCV13 serotypes causing IPD in adults stabilized in Portugal. The direct vaccination of adults may be important in preventing IPD in this age group.

Multiple clonal types of nonvaccine serotypes constitute β-lactams nonsusceptible pneumococcus isolates from adult pneumonia patients in Japan

Background and objective The global spread of antimicrobial-nonsusceptible Streptococcus pneumoniae is a major concern. Molecular epidemiology of those strains in relation to vaccine serotype remains to be explored in Japan. This study aimed to elucidate the distribution of molecular types with the serotypes and antimicrobial susceptibility of pneumococcus strains isolated from adult pneumonia patients. Methods We enrolled adult pneumonia patients from four sites in Japan between September 2011 and August 2014. S. pneumoniae isolates from sputum and blood were analyzed for serotyping by the Quellung reaction and for antimicrobial susceptibility by the agar dilution method and e-test and for multilocus sequence typing. Results In total, 204 isolates were analyzed from 200 patients with a median age of 72.5 years, of whom 55 (27.5%) patients had received a 23-valent pneumococcal polysaccharide vaccine (PPSV23). We detected 41 clonal complexes (CCs) and 62 sequence types (STs), including 10 new STs: CC/ST 180 of serotype 3 was the most common followed by CC/ST 236 of serotype 19F and CC/ST 99 of serotype 11A; 144 (70.6%) isolates were PPSV23 serotypes; 40 (19.6%) and 121 (59.3%) isolates were b-lactam nonsusceptible (bNS) and multidrug-nonsusceptible strains, respectively. Among the bNS strains, 18 (45%) were nonvaccine serotypes, and 4 CCs (CC236, CC63, CC242, and CC558) comprised of 62.5% of them.Conclusion Multiple CCs of bNS strains, including nonvaccine serotype are spreading. It is crucial to monitor the antimicrobial susceptibility, serotypes, and molecular types of pneumococci to predict the effectiveness of vaccines in preventing pneumonia by bNS pneumococci strains.