Polysaccharide Vaccine Research Articles

Impact of Influenza and Pneumococcal Polysaccharide Vaccination on Economic Burden from Acute Exacerbations of Chronic Obstructive Pulmonary Disease - Hebei Province, China, November 2018 to November 2020.

Chronic obstructive pulmonary disease (COPD) exacerbations increase household economic burden, but there is limited evidence from prospective cohort studies in China about the impact of vaccination on economic burden. This study demonstrated the economic burden of COPD exacerbations, pneumonia, and hospitalization in COPD patients in China is substantial. Influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately or together, were significantly associated with decreased economic burden. Our study supports evidence on recommendations that COPD patients in China are offered both influenza vaccine and PPSV23.

Safety and immunogenicity of sequential administration of PCV13 followed by PPSV23 in pneumococcal vaccine-naïve adults aged ≥ 65 years: Comparison of booster effects based on intervals of 0.5 and 1.0 year

ObjectiveAn open-label study was conducted to compare the safety and immunogenicity of a sequential administration of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) between an interval of 0.5 (0.5-y) and 1 year (1.0-y) in adults aged ≥ 65 years. MethodsPneumococcal vaccine-naïve adults aged ≥ 65 years (n = 129) received a sequential administration with an interval of 0.5-y or 1.0-y or received a single administration of PPSV23 (single PPSV23). We evaluated the immunogenicity before and 1 month after each vaccination and at 0.5-y intervals for 2 years. The primary endpoint was the increase in geometric mean fold rises (GMFRs) of immunoglobulin G (IgG) or opsonophagocytic activity (OPA) for eight common serotypes one month after one dose of PPSV23. The secondary endpoint was the safety profile for one dose of PPSV23. ResultsOne month after administration of PPSV23, the GMFRs of IgG considerably increased for five of eight serotypes in the 1.0-y interval group, whereas the GMFRs of IgG considerably increased for two serotypes in the 0.5-y interval group. Furthermore, GMFRs of OPA markedly increased for all eight serotypes in the 1.0-y interval group, while GMFRs of OPA markedly increased for four serotypes in the 0.5-y interval group. At 2 years after initial vaccination, GMFRs of IgG or OPA were higher for all serotypes, except for serotype 3, than those in the single PPSV23 group irrespective of intervals. No significant difference was found in the frequencies of local reactions of all grades between the two intervals. ConclusionsThe 1.0-y interval provided better booster effects induced by PPSV23 than those of the 0.5-y interval in a sequential administration in pneumococcal vaccine-naïve adults aged ≥ 65 years. No difference was found in the safety profile between both intervals.

Changes in Sputum Microbiocenosis and Clinical Pattern Under Different Vaccination Protocols for Pneumococcal Infection in Patients with Bronchial Asthma

Bronchial asthma is a serious public health issue. It is important to reduce the frequency of attacks for BA patients. Vaccination for pneumococcal infection is an important complementary tool that can improve the clinical pattern of bronchial asthma. The study involved 102 patients with bronchial asthma, who were monitored over 4 years. The patients were divided into 4 groups based on the vaccination scheme used for pneumococcal infection: PCV13, PPV23, PPV23/PCV13, PCV13/PPV23. Sequential vaccination with pneumococcal conjugate and polysaccharide vaccines leads to a decrease in the isolation of pneumococcus from sputum in BA patients, which has a pronounced positive effect on the clinical pattern of this disease, namely, it leads to a decrease in the frequency of attacks, the requirement for courses of antibacterial chemotherapy and hospitalizations, and therefore this vaccination protocol should be included in the standards of BA patient management.

Impact of vaccination with pneumococcal vaccines on recurrent pneumonia in patients with chronic obstructive pulmonary disease

Community-acquired pneumonia (САР) and chronic obstructive pulmonary disease (COPD) are among the main causes of mortality worldwide, and, in addition, they also lead to great economic losses for the health system of all countries. Currently, there is an increase in cases of recurrent pneumonia, both in the general population and, in particular, in patients with COPD. One of the most important risk factors for the development of pneumonia is the previous episode of САР. Potential risk factors for recurrent pneumonia are concomitant diseases such as heart failure, COPD, diabetes mellitus, neurological disorders, swallowing dysfunction, immune deficiency. To conduct a retrospective analysis of the effect of vaccine prophylaxis with conjugated pneumococcal vaccine (PCV13) and polysaccharide pneumococcal vaccine (PPV23) on the risk of recurrent pneumonia in patients with COPD. A total of 302 male patients were included in the retrospective study. When analyzing the data, the fact of the development of pneumonia of any etiology during the 5th observation period was taken into account. For the recurrence of pneumonia, more than two episodes of CAP were taken during the year. 13-valent conjugated pneumococcal vaccine Prevenar-13 and 23-valent polysaccharide vaccine Pneumo23 were used for vaccine prophylaxis. The relative risk of the event was calculated. A 95% confidence interval was used. A retrospective analysis showed that, firstly, CAP is a fairly frequent complication of COPD: initially, the average percentage of cases of САР was 19.3%. Secondly, the risk of developing repeated episodes of pneumonia remains quite high in unvaccinated patients and tends to increase within 5 years: from 17 to 22%. Thirdly, the pneumococcal vaccines used have different effects on the risk of recurrent pneumonia in patients with COPD, a significant decrease in the number of recurrent pneumonia is observed only with the use of conjugated vaccines.

Neisseria meningitidis Meningitis in Burkina Faso: Review of the Literature

Introduction: Neisseria meningitidis meningitis is a permanent threat in Burkina Faso due to its epidemic potential.
 Objective: To study the epidemiological aspects of meningitis caused by Neisseria meningitidis and to identify the main current trends. 
 Patients and Methods: This was a descriptive cross-sectional study with retrospective collection of data from the literature on Neisseria meningitidis epidemics in Burkina Faso. 
 Results: Burkina Faso has experienced several epidemics of meningitis caused by Neisseria meningitidis serogroup A. Indeed, the country was hit by epidemics due to this serogroup in 1957, 1985, 1994, 1995, 1996, 1997, 2004, 2005, 2006, 2007, 2008 and 2009. The 1996 epidemic was particularly deadly with 4363 deaths recorded. Neisseria meningitidis serogroup W has also been responsible for several epidemics including those of 1992, 2001, 2002, 2003, and 2012. While Neisseria meningitidis serogroup X was responsible for the first major epidemic in 2010. As for Neisseria meningitidis serogroup C, after a first outbreak in 1979, it was in 2019 that this serogroup was again responsible for an outbreak in eastern Burkina Faso. In all these outbreaks, children were the most affected and case fatality was high (more than 14%). In addition to the therapeutic management of cases, a vaccine response was used to contain these epidemics. The vaccines used were initially polysaccharide vaccines (meningococcal A+C vaccine, tetravalent A+C+Y+W vaccine), and since 2010, the MenAfriVac® conjugate vaccine, which has eliminated epidemics due to meningococcus (Nm) A. However, it is noted that other Neisseria meningitidis serogroups (X,C,W) continue to circulate. Epidemiological surveillance data showed a clear decline in Neisseria meningitidis in week 48 of 2022, behind Streptococcus pneumoniae which has become the leading cause of bacterial meningitis in Burkina Faso. The same trend has been observed since the mass vaccination campaign with the MenAfriVac® conjugate vaccine.
 Conclusion: The persistent circulation of Neisseria meningitidis serogroups W, X, and C raises concerns about further meningitis epidemics. It is important to maintain a high level of epidemiological surveillance of Neisseria meningitidis in Burkina Faso.

118. Rapid Uptake of 2014 ACIP Pneumococcal Vaccination Recommendations among Adults Aged 65 or Higher at the Veterans Health Administration

Abstract Background Vaccination of the 13-valent pneumococcal conjugate vaccine (PCV13) for adults 65 years and older was recommended by the Advisory Committee on Immunization Practices (ACIP) in 2014 until it was withdrawn in 2019. While estimated overall vaccination coverage rates with both vaccines at ∼30% were previously reported using data from surveys or Medicare claims, it is unclear how rapidly the uptake of this ACIP recommendation occurred. We aimed to describe the uptake of the ACIP among the Veterans Health Administration (VHA) population. Methods We conducted a retrospective cohort study of patients who were at 65 years or older in October 2014 who were registered in primary care of VHA. The study period was from October 2014 to November 2019. We obtained data on the first PCV13 and 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccination and dropout from primary care follow-up due to death and termination of primary care relationship from the VHA Corporate Data Warehouse. We calculated the monthly proportion of PCV13 and PPSV23 vaccination among primary care follow-up patients in VHA. Results We enrolled 2,166,173 patients at the beginning of the study period (median age: 73 (interquartile range: 68–81)), and at the end of the study period, 30% (645,975) were dropout due to death. The numbers of patients who had at least one PCV13 and PPSV23 vaccination at the beginning of the study period were 17,718 (0.8%) and 934,836 (43.2%), respectively. Of the PCV13 used during the study period, 78.4% were administered in the first two years (Figure 1). At the end of the study period, 50.3% of the follow-up patients had been vaccinated with PCV13 and 53.3% with PPSV23 (Figure 2). 55.3% of patients received at least one dose of any vaccine, and 48.2% received both. Figure 1.Administered dose of first PCV13 and PPSV23 among the study populationFigure 2.The proportion of vaccination coverage among the study population Conclusion At the VHA, there was a very rapid uptake of 2014 ACIP pneumococcal vaccination recommendations in the first two years, followed by a steady increase. At the end of the study period, the VHA achieved comparable or higher vaccination coverage in this population with both PCV13 and PPSV23 than the previously reported Medicare population. Further studies are needed to elucidate factors contributing to this rapid uptake and improve the implementation of future vaccine recommendations. Disclosures Michihiko Goto, MD MSCI, Merck & Co.: Grant/Research Support.

110. Improving Pneumococcal Vaccination in Patients Treated with Tumor Necrosis Factor-alpha Inhibitors: A Multidisciplinary Education-Based Quality Improvement Project

Abstract Background In 2012, pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23) were recommended for immunocompromised adults ≥19 years, but pneumococcal vaccination (PV) in these patients (pts) remains suboptimal. With a new PV (PCV20) allowing for simplified PV, we study rates of PV in pts on infliximab (INX) 1 year post-initiation of a pt and provider education-based quality improvement project aiming to increase PV in pts on Tumor Necrosis Factor-alpha inhibitors (TNF-αI). Methods Starting in 11/2020, pamphlets detailing PV indications were distributed to the Walter Reed National Military Medical Center infusion center and pharmacies to be given to pts prescribed/administered TNF-αI. Provider educational materials and pt pamphlets were given to services prescribing TNF-αI. Provider education was also offered to these services. Up to date (UTD) on PV was defined as receipt of PCV13 and PPSV23 (including additional PPSV23 dose ≥5 years post-initial PPSV23 if applicable). Ongoing INX (o-INX) was defined as INX initiation before 10/1/2020. Newly initiated INX (new-INX) was 10/1/2020-10/1/2021. One-year post implementation, we reviewed the PCV13 and PPSV23 immunization records of pts ≥19 years of age on INX from 1/1/21-12/31/21. This project was approved by the IRB under a non-research determination. Results 111 pts prescribed INX between 1/1/21-12/31/21 met inclusion criteria (87 o-INX and 24 new-INX). Prior to the intervention, of 87 o-INX pts, 45 (52%), 45 (52%), and 18 (21%) pts had received PCV13, ≥1 PPSV23 dose, and were UTD on PV respectfully. Between 1/1/21-12/31/21, 14 o-INX pts had PV (1 PCV13 and PPSV23, 7 PCV13, and 6 PPSV23), with 7 newly UTD (10% of the 69 previously not UTD), totaling 25 (29%) o-INX pts UTD on PV (figure 1). Of 24 new-INX pts, only 12 (48%), 9 (36%), and 6 (24%) had had PCV13, PPSV23, and were UTD on PV as of 12/31/21. No services prescribing TNF-αI requested the offered PV educational talks. Conclusion Despite frequent healthcare in a system where vaccination has no out of pocket expense, guideline-concordant PV was low in this cohort. With new, simplified PV, next steps include updated pt and targeted provider education. However, with prior small gains using multidisciplinary education, additional efforts to remove PV barriers may be needed. Disclosures Benjamin L. Custer, MD, Beam Therapeutics: Stocks/Bonds|CRISPR Therapeutics: Stocks/Bonds|glaxo-smith-kline: Stocks/Bonds|Hologic: Stocks/Bonds|Moderna: Stocks/Bonds|Pfizer: Stocks/Bonds|Regeneron: Stocks/Bonds|sanofi: Stocks/Bonds|Vertex Pharmaceuticals: Stocks/Bonds.

639. Vaccination in Kidney Transplant Candidates

Abstract Background Kidney transplant (KT) candidates have historically low immunization rates against recommended vaccines. A retrospective study of KT candidates was conducted to assess contemporary vaccination rates and vaccine uptake during pre-transplant evaluation. Methods All KT candidates ≥ 18 years referred to Transplant Infectious Disease Clinic for pre-transplant evaluation between January 1, 2020 and August 31, 2020 were retrospectively studied for history of prior vaccination against Tdap, 13 valent pneumococcal conjugate vaccine (PCV13), 23 valent pneumococcal polysaccharide vaccine (PPSV23), Hepatitis A and B (using Hepatitis A total IgG and Hepatitis B surface antibodies as surrogate markers) and recombinant zoster vaccine (RZV). Seropositivity (as a marker of immunity) against measles, mumps, rubella and varicella was also assessed. Results 109 KT candidates were evaluated (tables 1 & 2). Rates of prior vaccination against Tdap, PCV13 and PPSV23 were 33%, 58%, and 67%. Only 5 (8%) of 61 patients ≥ 50 years of age had received 2 doses of RZV. Thirty (28%) had positive Hepatitis A total IgG and 72 (66%) patients had a positive Hepatitis B surface antibody. Among 37 patients with negative Hepatitis B surface antibody, most had received at least one dose of Hepatitis B vaccine (five were non responders, 19 had had initiated the vaccine series and one had waning antibody response). 79-96% patients had immunity against measles, mumps, rubella and varicella. Patients ≥ 50 years (vs under 50 years) had numerically higher immunization rates against PCV13 and PPSV23 (67% vs 46% and 74% vs 58%) and higher rates of immunity against measles, mumps, rubella and varicella (95% vs 73%; 85% vs 69%, 95% vs 81% and 100% vs 92% respectively). Dialysis patients had a higher Hepatitis B surface antibody compared to non-dialysis patients (78% vs 39%). Only 6 of 109 patients were fully immunized. Among 103 vaccine eligible patients, 99 (96%) agreed to get vaccinated. Table 1Baseline characteristics of kidney transplant candidates Table 2 Vaccination in kidney transplant candidates Conclusion KT candidates have low rates of prior immunization against Tdap, PCV13, PPSV23, Hepatitis A and B and RZV but high rates of serological immunity against measles, mumps, rubella and varicella. The vaccine uptake during pre-transplant evaluation was high and it provides an unique opportunity to improve immunization in this population. Disclosures All Authors: No reported disclosures.

2115. Long Term Follow-up and Correlates of Success in Patients on Immune Globulin for Antibody Deficiency

Abstract Background Antibody deficiencies range from mild deficits of antibody subclasses to more severe deficiencies of all immune globulins. Patients with deficiencies of immune globulin G (IgG) are predisposed to recurrent sinopulmonary infections, often necessitating multiple courses of antibiotics and frequent hospitalizations and provider visits. Treatment with intravenous immune globulin (IVIG) replacement therapy is currently indicated for patients with severe primary immune deficiencies but is less well studied in patients with more mild deficits that nonetheless experience recurrent infections. Methods A retrospective chart review was conducted on 71 patients from the Temple University Infectious Disease Department (15 transplant recipients) with varying levels of antibody deficiency that had been treated with monthly IVIG for at least six months. Available patients (N=49) were interviewed by phone about their experiences on IVIG, side effects, and quality of life changes on therapy. Results Mean age sx onset was 40 y,68% were women, 87% Caucasian, 49% had pneumonia, 65% purulent bronchitis, 65% sinusitis. Patients reported a mean reduction in infection frequency of 78% and average patient-reported improvement in quality of life was 4.7/5.0. Antibody deficiency levels at baseline were not correlated with infection reduction (R=-.05, p=0.71), Figure 1 and neither was response to pneumococcal polysaccharide vaccine (vaccine responder median infection reduction 83%; non responder 87%, p= 0.60) Figure 2. Adverse events on treatment were experienced by 59% of patients and caused 9 patients (13%) to stop treatment. There was no difference in incidence of adverse events between men and women (p= 0.076), but women had a 50% higher rates of severe headache than men (p= 0.038); 10% pts required a port or PICC, 32% IV fluids, 48% IV steroids, 31% IVIG brand change; 17% changed to subcutaneous IG. Figure 1:Pre-treatment Antibody Deficit and Infection Reduction by IVIGPlot of percent deficit of most deficient antibody subclass against infection reduction by IVIG (% of yearly pre-IVIG infections)Infection Reduction by IVIG According to Vaccine Responsiveness Box plot of percent infection reduction after IVIG according to response to polysaccharide vaccine Conclusion Even patients with relatively mild immunoglobulin deficiencies can experience a significant reduction in recurrent infections and improved quality of life when treated with immunoglobulin. IVIG is usually well tolerated for many years but may require adjunctive steroids, IV hydration, or brand change to limit adverse side effects. Disclosures All Authors: No reported disclosures.

Immunogenicity of three versus four doses of 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine in allogeneic haematopoietic stem cell transplantation recipients: a multicentre, randomized controlled trial

ObjectiveThis multicentre, phase 2, randomized, controlled study of allogeneic haematopoietic stem cell transplantation (allo-HSCT) recipients compared the immunogenicity of two anti-pneumococcal vaccine regimens: four doses of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) (3+1+1 experimental group), and three doses of PCV13 followed by PPSV23 (3+0+1 group). MethodsAllo-HSCT recipients without active graft-versus-host disease at enrolment were eligible. The primary endpoint was the IgG response rate (≥0.20 mg/mL) for all eight measured serotypes at 5 months after the PPSV23 booster. ResultsSeventy-two recipients were randomized, and seventy recipients who received over one PCV13 dose were analysed. The mean ages were 47.2 years (standard deviation, 14.4) in the 3+1+1 group (n = 35) and 49.0 years (standard deviation, 14.3) in the 3+0+1 group (n = 35). There was no significant difference in the overall IgG response rate at 5 months after the PPSV23 booster between the 3+1+1 and 3+0+1 groups (100% (26/26) vs. 93% (27/29), respectively, relative risk (RR): 1.07; 95% confidence interval (CI): 0.97–1.19). This rate was high immediately before the PPSV23 booster in the 3+1+1 group (100% (26/26) compared with 81% (21/26), respectively, RR: 1.24; 95% CI: 1.03–1.49), but this difference disappeared 1 month after the PPSV23 booster (100% (26/26) vs. 97% (28/29), respectively, RR: 1.04; 95% CI; 0.97–1.11). No serious adverse events leading to study dropout occurred. DiscussionWe were not able to determine the efficacy of the experimental arm based on the IgG response rate at 5 months after the PPSV23 booster in allo-HSCT recipients.

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in Denmark compared with PPV23

Background A new 20-valent pneumococcal conjugate vaccine (PCV20) provides protection against 20 pneumococcal serotypes. The vaccine has the potential to decrease the impact of pneumococcal diseases in society and to increase health among vulnerable persons. Aim This study investigates the cost-effectiveness of vaccinating Danish adults in different age groups and risk of pneumococcal disease with PCV20 compared to the 23-valent pneumococcal polysaccharide vaccine (PPV23) – either as PCV20 compared to PPV23 or as PPV23 followed by PCV20 compared to PPV23. Methods A Markov model adapted to the Danish setting was developed to estimate clinical outcomes and costs of vaccinating the Danish population in specific age and risk groups. The model used a restricted societal perspective and estimated outcomes and costs using a lifetime time horizon. To estimate the clinical outcomes and costs, inputs on vaccine effectiveness and waning were retrieved from other studies whereas data on risk groups, coverage and costs were based on real-world data. Results The results showed that in all scenarios the incidence and mortality of pneumococcal disease were reduced when vaccinating with PCV20, resulting in lower costs. For the vaccine target group of adults aged ≥18 years at moderate or high risk and all adults aged ≥65 years both in the case of PPV23+PCV20 compared to PPV23 and in case of PCV20 compared to PPV23 vaccination with PCV20 was found to be a dominant strategy gaining 1,350 or 5,821 quality-adjusted life years (QALYs), respectively, and reducing total costs by 60 or 396 million EUR, respectively, as compared to PPV23 vaccination alone. Similar results of dominant PCV20 strategy were found for other age and risk group comparisons. Both deterministic and probabilistic sensitivity analyses confirmed the results being robust to changes in input parameters and applied assumptions. Limitations Like other modelling studies, this analysis has limitations such as lack of detailed data for some inputs. Conclusion Vaccination with PCV20 reduced the incidence and mortality of pneumococcal diseases in Danish adults compared to PPV23. This reduction has the potential to reduce the financial burden related to managing diseases while also increasing public health.

EE188 Health and Economic Impact of 23-Valent Pneumococcal Polysaccharide Vaccine in the Older Adult Immunization Program in Mexico

EE188 Health and Economic Impact of 23-Valent Pneumococcal Polysaccharide Vaccine in the Older Adult Immunization Program in Mexico

EE390 Cost-Effectiveness of the 20-Valent Pneumococcal Conjugate Vaccine vs 15-Valent Pneumococcal Conjugate Vaccine for Adults in Argentina

Assess the cost-effectiveness of a single dose of 20-valent pneumococcal conjugate vaccine (PCV20) versus sequential administration of sequential administration of PCV15 followed by pneumococcal polysaccharide vaccine (PPV23) in the adult population of Argentina.

Caveolae-Mediated Extracellular Vesicle (CMEV) Signaling of Polyvalent Polysaccharide Vaccination: A Host-Pathogen Interface Hypothesis.

We published a study showing that improvement in response to splenectomy associated defective, in regards to the antibody response to Pneumovax® 23 (23-valent polysaccharides, PPSV23), can be achieved by splenocyte reinfusion. This study triggered a debate on whether and how primary and secondary immune responses occur based on humoral antibody responses to the initial vaccination and revaccination. The anti-SARS-CoV-2 vaccine sheds new light on the interpretation of our previous data. Here, we offer an opinion on the administration of the polyvalent polysaccharide vaccine (PPSV23), which appears to be highly relevant to the primary vaccine against SARS-CoV-2 and its booster dose. Thus, we do not insist this is a secondary immune response but an antibody response, nonetheless, as measured through IgG titers after revaccination. However, we contend that we are not sure if these lower but present IgG levels against pneumococcal antigens are clinically protective or are equally common in all groups because of the phenomenon of "hyporesponsiveness" seen after repeated polysaccharide vaccine challenge. We review the literature and propose a new mechanism-caveolae memory extracellular vesicles (CMEVs)-by which polysaccharides mediate prolonged and sustained immune response post-vaccination. We further delineate and explain the data sets to suggest that the dual targets on both Cav-1 and SARS-CoV-2 spike proteins may block the viral entrance and neutralize viral load, which minimizes the immune reaction against viral attacks and inflammatory responses. Thus, while presenting our immunological opinion, we answer queries and responses made by readers to our original statements published in our previous work and propose a hypothesis for all vaccination strategies, i.e., caveolae-mediated extracellular vesicle-mediated vaccine memory.

A highly immunogenic vaccine platform against encapsulated pathogens using chimeric probiotic Escherichia coli membrane vesicles

Vaccines against infectious diseases should elicit potent and long-lasting immunity, ideally even in those with age-related decline in immune response. Here we report a rational polysaccharide vaccine platform using probiotic Escherichia coli-derived membrane vesicles (MVs). First, we constructed a probiotic E. coli clone harboring the genetic locus responsible for biogenesis of serotype 14 pneumococcal capsular polysaccharides (CPS14) as a model antigen. CPS14 was found to be polymerized and mainly localized on the outer membrane of the E. coli cells. The glycine-induced MVs displayed the exogenous CPS14 at high density on the outermost surface, on which the CPS14 moiety was covalently tethered to a lipid A-core oligosaccharide anchor. In in vivo immunization experiments, CPS14+MVs, but not a mixture of free CPS14 and empty MVs, strongly elicited IgG class-switch recombination with a Th1/Th2-balanced IgG subclass distribution without any adjuvant. In addition, CPS14+MVs were structurally stable with heat treatment and immunization with the heat-treated MVs-elicited CPS14-specific antibody responses in mouse serum to levels comparable to those of non-treated CPS14+MVs. Notably, the immunogenicity of CPS14+MVs was significantly stronger than those of two currently licensed vaccines against pneumococci. The CPS14+MV-elicited humoral immune responses persisted for 1 year in both blood and lung. Furthermore, the CPS14+MV vaccine was widely efficacious in mice of different ages. Even in aged mice, vaccination resulted in robust production of CPS14-specific IgG that bound to the pneumococcal cell surface. Taken together, the present probiotic E. coli MVs-based vaccine platform offers a promising, generalizable solution against encapsulated pathogens.

Cost-Effectiveness of Pneumococcal Vaccination among Patients with Diabetes Mellitus

Relevance. Patients with diabetes mellitus have an increased risk of developing various infections, including those of the lower respiratory tract. Immunization with anti-pneumococcal vaccines reduces pneumonia-related hospitalizations and deaths.Aim. Evaluate the cost-effectiveness of vaccination against pneumococcal infection in 40and 65-year-old patients with type 2 diabetes mellitus (DM2).Material and methods. The analysis was carried out from the perspective of the healthcare system. The Markov model based on Russian epidemiological data, taking into account the results of foreign studies, was used. Vaccination schedules with 1 dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 1 dose of pneumococcal 23-valent polysaccharide vaccine (PPV23) and vaccination with only 1 dose of PCV13 were evaluated. The time horizon of the study is 5 years. Costs and life expectancy were discounted by 3.5% per year.Results. Vaccination of 65-year-old patients with type 2 diabetes is characterized by extremely high cost-effectiveness (the incremental cost effectiveness ratio – ICER – for PCV13+PPV23 vaccination is 189.27 thousand rubles/QALY, and PCV13 vaccination entails a cost reduction of 371.92 rubles per 1 vaccinated). When vaccinating 40-year-old patients, the ICER for PCV13 + PPV23 vaccination is 491.31 thousand rubles/QALY, and for PCV13 – 55.31 thousand rubles/QALY.Conclusion. Vaccination against pneumococcal disease in 40and 65-year-old patients with DM2 reduces the associated morbidity and mortality and is highly cost-effective. Compared to PCV13 vaccination alone, vaccination with PCV13 followed by the introduction of PPV23 provides an increase in the number of prevented cases of the disease and the deaths caused by it, but at the same time requires additional costs.

30-Minute Highly Multiplexed VaxArray Immunoassay for Pneumococcal Vaccine Antigen Characterization.

Pneumonia accounts for over 20% of deaths worldwide in children aged 1 to 5 years, disproportionately affecting lower- and middle-income countries. Effective, highly multivalent pneumococcal vaccines are available to decrease disease burden, with numerous new vaccines currently under development to serve a variety of worldwide markets. However, pneumococcal conjugate vaccines are among the hardest biologics to manufacture and characterize due to their complexity and heterogeneity. Current characterization methods are often inherently singleplex, requiring separate tests for each serotype present. In addition, identity and quantity are often determined with separate methods. We developed the VaxArray pneumococcal assay for applications in identity, quantity, and stability testing of pneumococcal polysaccharide and pneumococcal conjugate vaccines. The VaxArray pneumococcal assay has a time to result of less than 30 min and is an off-the-shelf multiplexed, microarray-based immunoassay kit that can identify and simultaneously quantify 23 pneumococcal polysaccharide serotypes common to many on-market and in-development vaccines. Here, we highlight the potential of the assay for identity testing by showing high reactivity and serotype specificity to a wide variety of native polysaccharides, CRM197-conjugated polysaccharides, and drug product. The assay also has vaccine-relevant lower limits of quantification in the low-to-mid ng/mL range and can be used for accurate quantification even in adjuvanted vaccines. Excellent correlation to the anthrone assay is demonstrated, with VaxArray resulting in significantly improved precision over this antiquated chemical method.

Specific antibody deficiency to pneumococcal polysaccharide in a young adult with recurrent respiratory infections: a case report.

Specific antibody deficiency against pneumococcal serotypes was detected in a patient with recurrent episodes of fever. A 21-year-old man presented with a two-month history of recurrent episodes of fever and shaking chills. He was diagnosed with recurrent episodes of pneumonia caused by Streptococcus pneumoniae serotype 19A and treated with amoxicillin. Serotype-specific antibodies were not produced against most of the serotypes, which were consistent with moderate specific antibody deficiency. After pneumococcal 13-valent conjugate vaccination and pneumococcal polysaccharide vaccination, he adequately responded to the infecting serotype with an antibody titer of 1.1 µg/mL. There were eventually no recurrent episodes of fever with pneumonia.

Immunogenicity of the Currently Recommended Pneumococcal Vaccination Schedule in Patients with Chronic Lymphocytic Leukaemia

Background Patients with chronic lymphocytic leukemia (CLL) are at increased risk of both invasive pneumococcal disease (IPD) and community acquired pneumonia (CAP) caused by Streptococcus pneumoniae. Therefore, international guidelines recommend pneumococcal vaccination for all CLL patients, preferably before initiation of treatment. The vaccination schedule recommended in the European Conference on Infections in Leukaemia (ECIL) 7 guideline consists of Prevnar13®, a 13-valent pneumococcal conjugated vaccine (PCV13) followed 2 months later by Pneumovax23®, a 23-valent polysaccharide vaccine (PPSV23). However, the immunogenicity of this sequential pneumococcal vaccination schedule in CLL patients is unknown. The aim of this study is to assess the immunogenicity of PCV13 followed by PPSV23 in untreated and treated CLL patients, as CLL treatment has been shown to be a major determinant of COVID-19 vaccine immunogenicity. Methods We quantified pneumococcal immunoglobulin G (IgG) concentrations to 5 pneumococcal serotypes shared across both vaccines (6B, 9V, 14, 19F, 23F) and 4 serotypes unique to PPSV23 (8, 15B, 20, 33F) before and 4-8 weeks after vaccination using a validated multiplex immunoassay, Luminex®. The primary outcome was the serologic response rate (SRR), defined as a ≥4-fold increase in ≥70% of the serotype-specific anti-pneumococcal IgGs. Secondary outcome was serologic protection, defined as an antibody concentration of ≥1.3 mcg/ml for ≥70% of all measured serotypes, in accordance with the definition by the American Academy of Allergy, Asthma & Immunology. Additional secondary outcomes were serotype-specific serologic protection and IgG level dynamics. Results We included 113 CLL patients (mean age 66 years; 39/113 female) in one academic and six teaching hospitals in the Netherlands. All completed the vaccination and measurement schedule. Median time since CLL diagnosis was 3.6 years. Of the 113 patients 33 had previously received CLL treatment, including rituximab (22 patients), cytotoxic chemotherapy (11), ibrutinib (10) and/or venetoclax (7). Seven patients received intravenous immunoglobulin prior to the vaccinations, while 6 received this during the vaccination scheme. The SRR was 11.5% (15% in untreated and 3% in treated patients) (Table 1). A statistically significant increase in all serotype-specific antibody concentrations was observed after vaccination (p <0.001) (Figure 1). The immunogenicity varied per serotype: the percentage of patients mounting a 4-fold increase was lowest for serotype 20 (16%) and highest for serotype 9V (40%). The serotype-specific anti-pneumococcal IgGs after vaccination were all significantly lower in treated than in previously untreated patients. Nevertheless, treatment status was not statistically significant associated with the SRR. Total IgG concentration prior to vaccination was the only evaluated factor associated with the SRR (OR 5.69; p = 0.008). Serologic protection increased from 1.8% before vaccination to 10.6% after both vaccinations (13.8% in untreated and 3% in treated patients). Serotype-specific protection was highest for serotype 14 and 33F (43.4% of patients obtained a concentration of ≥1.3 mcg/ml) and lowest for serotype 6B (16.8%). Conclusion The serologic response to combined PCV13 and PPSV23 vaccination is impaired in previously treated CLL patients as well as in treatment-naive patients, a contrast with COVID-19 vaccination. These findings emphasize the importance of further investigation into the pneumococcal vaccination response in CLL patients. Since patients with CLL are insufficiently protected after a single dose of PCV13, research should focus on multi-dose PCV schedules with the currently available higher valent T cell dependent conjugate vaccines. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Immunogenicity of a 20-valent pneumococcal conjugate vaccine in adults 18 to 64 years old with medical conditions and other factors that increase risk of pneumococcal disease

ABSTRACT The aim of this post hoc analysis was to describe the immunogenicity of the 20-valent pneumococcal conjugate vaccine (PCV20) in adults with chronic medical conditions or smoking that place them at increased risk of developing pneumococcal disease. Data from 2 phase 3, randomized, active-controlled, double-blind studies in pneumococcal vaccine-naive adults were analyzed. Study 1: adults ≥18 years were enrolled in 1 of 3 age-based cohorts (18‒49, 50‒59, and ≥60 years) and randomized (1:1, adults ≥60 years; 3:1, younger cohorts) to receive 1 dose of PCV20 or 13-valent PCV (PCV13). Participants ≥60 years who received PCV13 were administered 23-valent polysaccharide vaccine 1 month later. Study 2: adults 18‒49 years were randomized (2:2:2:1) to receive 1 dose of PCV20 from 1 of 3 lots or PCV13. Opsonophagocytic activity (OPA) titers were measured in sera collected before and 1 month after vaccination. We investigated immune responses of PCV20 among participants 18‒64 and 18‒49 years of age with ≥1 medical condition or other factor (smoking) that increases the risk of serious pneumococcal disease. Of 4369 participants overall (PCV20, n = 2975; PCV13, n = 1394), 1329 participants (30%) had ≥1 risk factor; most commonly smoking, diabetes, and chronic pulmonary disease. Among participants with risk factors, substantial increases in OPA geometric mean titers were observed across the 20 vaccine serotypes from before vaccination to 1 month after PCV20. Robust immune responses to all 20 vaccine serotypes 1 month after PCV20 were observed in adults with increased risk of serious pneumococcal disease. Clinical trial registration NCT03760146, NCT03828617.