Polysaccharide Vaccine Research Articles

Cost-Effectiveness Analysis of the Use of V116, a 21-Valent Pneumococcal Conjugate Vaccine, in Vaccine-Naïve Adults Aged ≥ 65 Years in the United States.

Given the recent approval and recommendation of V116, a 21-valent pneumococcal conjugate vaccine (PCV), in the United States(US), we evaluated the cost-effectiveness of using V116 versus the 20-valent PCV(PCV20) or the 15-valent PCV(PCV15) in series with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) among adults aged ≥ 65years in the US who had never received a PCV previously. A static multi-cohort state-transition Markov model was developed to estimate the lifetime incremental clinical and economic impact of V116 vs. PCV20 or PCV15 + PPSV23 from the societal perspective. All model inputs were based on published literature and publicly available databases and/or reports. Model outcomes included undiscounted clinical cases: invasive pneumococcal disease (IPD), inpatient and outpatient non-bacteremic pneumococcal pneumonia (NBPP), post-meningitis sequelae (PMS), deaths from IPD and inpatient NBPP, discounted quality-adjusted life years (QALYs) as well as the discounted total cost (in 2023 USD), which consisted of vaccine acquisition and administration costs, direct and indirect costs associated with the disease, and travel costs for vaccination. The final summary measure was the incremental cost-effectiveness ratio (ICER), reported as $/QALY gained. Three percent was used for the annual discounting rate. Based on the inputs and assumptions used, the results indicated that the V116 strategy prevented 27,766 and 32,387 disease cases/deaths and saved $239 million and $1.8 billion in total costs when compared to the PCV20andPCV15 + PPSV23 strategies, respectively, in vaccine-naïve adults aged ≥ 65years. The estimated ICERs were cost saving in both regimens (i.e., V116 vs. PCV20 or vs. PCV15 + PPSV23). The scenario analysis and deterministic and probabilistic sensitivity analyses also demonstrated the robustness of the qualitative results. These results demonstrated that using V116 in adults aged ≥ 65years in the US can prevent a substantial number of PD cases and deaths while remaining highly favorable economically over a wide range of inputs and scenarios.

Polysaccharide, Conjugate, and mRNA-based Vaccines are Immunogenic in Patients with Netherton Syndrome

BackgroundNetherton syndrome (NS) is a rare, severe genetic skin disorder, currently classified as an inborn error of immunity (IEI) due to previously reported immune dysregulation. We recently reported the results of an immunological evaluation showing no evidence for a relevant B- and/or T-cell mediated immunodeficiency, but immune responses after vaccination were not evaluated in that study. Therefore, we evaluated immune responses to three vaccine platforms in adult NS patients to further investigate the presence of a clinically relevant B- and/or T-cell immunodeficiency.MethodsVaccination responses in eight adult NS patients were assessed in a cross-sectional study performed between January and August 2022. Clinical patient data were retrospectively retrieved from electronic patient files. Immune responses to a polysaccharide Streptococcus pneumoniae vaccine (PPV23) and conjugate Haemophilus influenzae type b vaccine (ActHiB) were measured. SARS-CoV-2-specific (functional) antibody and T-cell responses following booster vaccination with an mRNA-based COVID-19 vaccine were compared to controls.ResultsNone of the included patients suffered from recurrent and/or severe infections that could be attributed to a B- and/or T-cell immunodeficiency. ActHiB induced immune responses were normal in 7/7 NS patients. PPV23 induced responses were absent in 1/7, diminished in 2/7, and normal in 4/7 patients. Levels of SARS-CoV-2-specific binding and neutralizing antibodies after mRNA-based COVID-19 booster vaccination in NS patients were comparable to controls. SARS-CoV-2-specific CD4 + T-cell responses were detectable in all NS patients. In contrast, SARS-CoV-2-specific CD8 + T-cell responses were detectable in only 2/6 NS patients. T-cell responses to a positive control antigen pool were comparable to controls.ConclusionsVaccine-induced immune responses were detectable after polysaccharide, conjugate and mRNA-based vaccination in our cohort of NS patients. A spectrum of responsiveness to vaccine challenges was found, with the ranges of vaccine responses overlapping those demonstrated in healthy control populations.

Vaccinations in pulmonary diseases - part 2: herpes zoste, RSV, pneumococcal infection and pertussis

RSV is a common cause of respiratory tract infections, posing a risk of severe disease, particularly for newborns and infants, as well as in older individuals with pre-existing conditions. Two safe and effective RSV vaccines were approved in 2023. These vaccines elicit protective antibodies and offer robust protection with no additional benefit from annual boosters. Both vaccines have been approved for individuals aged 60 years and older, while one of the vaccines has also been approved in pregnant women to elicit maternal immunity for passive protection of the unborn child. In Germany, RSV vaccination is currently recommended for all individuals aged 75 years and older, as well as people aged 60-74 years of age with severe underlying conditions. PNEUMOCOCCAL INFECTION: Streptococcus pneumoniae is a primary cause of community-acquired pneumonia (CAP). Since early 2022, a 20-valent conjugate vaccine (PCV20) is approved and recommended for people over 60 years of age and individuals over 18 years of age with risk factors. PCV20 replaces the 23-valent polysaccharide vaccine (PPV23) previously recommended for those over 60 years of age. Although viewed primarily as a childhood disease, the majority of infections affect adults. Patients with chronic respiratory diseases are at a higher risk for severe clinical course of pertussis infection. It has therefore been recommended that all adults should get a pertussis booster with their next scheduled tetanus vaccination, given as a combination vaccine (Tdap). For risk groups (healthcare personnel, community facilities) a booster vaccination every 10 years is recommended. Herpes Zoster (shingles) is caused by the varicella-zoster virus, and reactivations can lead to painful skin lesions and potential complications such as herpes zoster oticus, meningitis, or postherpetic neuralgia. People with chronic lung diseases such as COPD or asthma are at increased risk of herpes zoster-related complications. A recombinant adjuvanted inactivated vaccine was approved in 2018 and offers robust protection against herpes zoster and its complications. The vaccine is recommended for all people over 60 years of age and for certain risk groups over 50 years of age.

Impact of PCV13 and PPSV23 Vaccination on Invasive Pneumococcal Disease in Adults with Treated Rheumatoid Arthritis: A Population-Based Study

On-time receipt of pneumococcal vaccines is essential in patients with rheumatoid arthritis (RA) as immunosuppressive medications increase their risk of invasive pneumococcal disease (IPD). However, data regarding the impact of timely administration of these vaccines on the risk of developing IPD are lacking for RA patients. We conducted a retrospective cohort study to assess the impact of on-time vaccination for pneumococcal conjugate vaccine (PCV) 13 and pneumococcal polysaccharide vaccine (PPSV) 23 in patients treated for RA on the development of IPD using national Veterans Affairs data from 2010 to 2018. Patients > 18 years of age, diagnosed with RA, and newly initiated on RA treatment were included. Pneumococcal vaccine compliance was assessed by measuring on-time receipt of PCV13 and PPSV23 vaccinations. A total of 33,545 patients were included in the cohort. Non-compliance with PCV recommendations was associated with an increased risk of IPD in a multivariable logistic regression model. This finding was consistent whether IPD status was ascertained by International Classification of Diseases coding (OR 2.42, 95%CI 2.14–2.73) or microbiologic data (OR 1.64, 95%CI 1.26–2.14). Providers should actively seek opportunities to provide pneumococcal vaccinations to patients with RA, as their on-time administration is associated with a decreased risk of IPD.

Immunization with recombinant Streptococcus pneumoniae PgdA protects mice against lung invasion.

Current pneumococcal vaccines, including the pneumococcal polysaccharide (PPV23) and conjugate (PCV13) vaccines, offer protection against specific serotypes but pose risks of serotype replacement that can alter the composition of the nasopharyngeal microbiota. To address this challenge, a novel strategy has been proposed to provide effective protection without disrupting the colonization of other bacterial populations. In our study, we found that subcutaneous immunization with recombinant peptidoglycan N-acetylglucosamine deacetylase A (rPgdA) elicited robust humoral and cellular immune responses, significantly reducing the invasion of Streptococcus pneumoniae in the lungs without affecting nasopharyngeal carriage. Furthermore, rPgdA antisera were shown to diminish bacterial invasion of lung epithelial cells in vitro. Notably, sera from patients with invasive pneumococcal infections exhibited higher levels of antibodies against the PgdA protein compared to sera from healthy adults, suggesting that a natural immune response to this protein occurs during infection. These results suggest a promising new target for the development of pneumococcal vaccines.

Capvaxive - A 21-valent pneumococcal conjugate vaccine.

The FDA has licensed Capvaxive (PCV21; Merck), a 21-valent pneumococcal conjugate vaccine, for prevention of invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults. Four other pneumococcal vaccines are currently available in the US: Prevnar 20 (PCV20), Vaxneuvance (PCV15), and Prevnar 13 (PCV13) are conjugate vaccines licensed for use in persons ≥6 weeks old, and Pneumovax 23 (PPSV23) is a pneumococcal polysaccharide vaccine licensed for use in persons ≥2 years old.

How effective is 13-valent pneumococcal conjugate vaccine (PCV13) combined with 23-valent pneumococcal polysaccharide vaccine (PPSV23)?

The bacterium Streptococcus pneumoniae remains a major causeof morbidity and mortality worldwide. Currently, the 2 leading vaccines targeted against it are: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). It was only very recently, starting 22 November 2019, that the Advisory Committee on Immunisation Practices (ACIP) no longer recommends routine administration of PCV13 for all adults aged 65 and above. As such, this systematic review aims to investigate how the use of PCV13 combined with PPSV23 compares to using PPSV23 alone in older adults. Relevant research papers were chosen through an electronic searchin PubMed. A set of selection criteria was then applied to ensure that the papers aligned with the objectives of this paper. The majority of the studies included in this paper demonstrated that in adults aged 50 years and above, PCV13 had the ability to generate a strong immune response in adults, even more so than PPSV23 for all of the twelve serotypes common to both vaccines. The safety of PCV13 was also demonstrated in the studies as no PCV13-related serious adverse events (SAEs) had surfaced. Only one study included in this systematic review opposed the trend.While the evidence for both PCV13’s and PPSV23’s ability to generate an immune response have been persuasive, more research that focuses on the clinical endpoint in older adults, as well as the incidence of pneumococcal infections in the population, could be done to fully address the main question of this paper.

Comparison of short- and long-term humoral immune responses to pneumococcal polysaccharide and glycoconjugate vaccines in an HIV-infected population

Immunisation is recommended internationally to protect against pneumococcal infections in HIV-infected adults. However, vaccination schedule designs are mostly based on studies of initial rather than long-term antibody responses. This UK observational study investigated the short- and long-term antibody responses to polysaccharide and glycoconjugate pneumococcal vaccines in an adult HIV-infected cohort. We studied a subgroup of 152 of 839 participants from the AIR (Assessment of Immune Responses to Routine Immunisations in HIV-infected Adults, ISRCTN95588307) studythat had received pneumococcal vaccinationsand had blood samples collected pre- and post-vaccination, as well as at least annually for four subsequent calendar years. Patients received either Pneumovax-23 (PPV, N=89) or Prevenar-13 (PCV, N=63) as their primary vaccine, with immunity assessed by measuring IgG antibody concentrations for 12 pneumococcal polysaccharide serotypes (PnPS). The primary outcome was achieving IgG antibody concentrations above the recommended World Health Organisation (WHO) threshold of 0.35µg/mL for at least 8/12 of the PnPS assessed (WHO≥8/12PnPS). Patients who did not achieve WHO≥8/12PnPS after the primary vaccination were offered further vaccination with PCV; booster vaccinations with PCV were additionally offered to those where antibody levels subsequently fell below the WHO≥8/12PnPS threshold. Patients receiving PCV as their primary pneumococcal vaccine were significantly more likely to achieve WHO≥8/12PnPS after a single vaccine dose than those receiving PPV (54% vs. 33%, p=0.012). This difference persisted following booster vaccination with PCV, with cumulative rates of WHO≥8/12PnPS in those receiving PCV vs. PPV as the primary vaccine of 88% vs. 67% and 100% vs. 85% after receiving up to one and two booster vaccinations, respectively. Where WHO≥8/12PnPS was achieved, this persisted significantly longer in those receiving PCV as their primary vaccine compared to PPV (median: 23.5 vs. 11.1 months; p=0.010). Immunisation with PCV resulted in quantitatively greater antibody responses than immunisation with PPV in a cohort of HIV-infected UK adults. Individuals receiving PCV as their primary vaccine required fewer total pneumococcal vaccine doses to achieve WHO≥8/12PnPS and experienced greater duration of time above this threshold than those with PPV as the primary vaccine. However, the median longevity of both vaccine responses was relatively short, which supports the use of ongoing booster doses using high-valency glycoconjugate vaccines to sustain WHO≥8/12PnPS threshold antibody levels.

Immunogenicity of Pneumococcal Polysaccharide Vaccine in patients with rheumatoid arthritis

The presented review searched for articles in the databases PubMed, Web of Science, Scopus, Google Scholar, eLibrary (2002-2022) and assessed the immunogenicity of the 23-valent polysaccharide pneumococcal vaccine (PPV23) in adult patients with rheumatoid arthritis (RA), receiving various antirheumatic drugs. The results of this review indicated sufficient immunogenicity of PPV23 in RA patients receiving monotherapy with various biological drugs (bDMARDs) (TNFα inhibitors, IL6 receptor inhibitors, T-lymphocyte costimulation blockers), targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and glucocorticoids (GC) in medium and low doses. Monotherapy with methotrexate (MTX), rituximab and combination therapy with bDMARDs +MTX, tsDMARDs+MTX in RA patients reduced the postvaccination pneumococcal response. IgG AT generated in response to PPV23 injection shown functional activity even in RA patients whose antibodies were either lowered in patients receiving MTX or were not detectable at protective values following bDMARD therapy. The potential for pneumococcus antibody production in RA patients receiving therapy with disease-modifying antirheumatic drugs (DMARDs), tsDMARDs and bDMARDs, was concluded. Vaccination against pneumococcal infection should be advised prior to starting therapy due to the likelihood of low antibody levels developing during rituximab treatment.

An intranasal cationic liposomal polysaccharide vaccine elicits humoral immune responses against Streptococcus pneumoniae

Diseases caused by S. pneumoniae are the leading cause of child mortality. As antibiotic resistance of S. pneumoniae is rising, vaccination remains the most recommended solution. However, the existing pneumococcal polysaccharides vaccine (Pneumovax® 23) proved only to induce T-independent immunity, and strict cold chain dependence of the protein conjugate vaccine impedes its promotion in developing countries, where infections are most problematic. Affordable and efficient vaccines against pneumococcus are therefore in high demand. Here, we present an intranasal vaccine Lipo+CPS12F&αGC, containing the capsular polysaccharides of S. pneumoniae 12F and the iNKT agonist α-galactosylceramide in cationic liposomes. In BALB/cJRj mice, the vaccine effectively activates iNKT cells and promotes B cells maturation, stimulates affinity-matured IgA and IgG production in both the respiratory tract and systemic blood, and displays sufficient protection both in vivo and in vitro. The designed vaccine is a promising, cost-effective solution against pneumococcus, which can be expanded to cover more serotypes and pathogens.

Use of 21-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Recommendations of the Advisory Committee on Immunization Practices - United States, 2024.

On June 17, 2024, the Food and Drug Administration approved 21-valent pneumococcal conjugate vaccine (PCV) (PCV21; CAPVAXIVE; Merck Sharp & Dohme, LLC) for adults aged ≥18 years. PCV21 does not contain certain serotypes that are included in other licensed pneumococcal vaccines but adds eight new serotypes. The Advisory Committee on Immunization Practices (ACIP) recommends use of a PCV for all adults aged ≥65 years, as well as adults aged 19-64 years with certain risk conditions for pneumococcal disease if they have not received a PCV or whose vaccination history is unknown. Previously, options included either 20-valent PCV (PCV20; Prevnar20; Wyeth Pharmaceuticals, Inc.) alone or a 15-valent PCV (PCV15; VAXNEUVANCE; Merck Sharp & Dohme, LLC) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23; Merck Sharp & Dohme, LLC). Additional recommendations for use of PCV20 exist for adults who started their pneumococcal vaccination series with 13-valent PCV (PCV13; Prevnar13; Wyeth Pharmaceuticals, Inc.). The ACIP Pneumococcal Vaccines Work Group employed the Evidence to Recommendations framework to guide its deliberations on PCV21 vaccination among U.S. adults. On June 27, 2024, ACIP recommended a single dose of PCV21 as an option for adults aged ≥19 years for whom PCV is currently recommended. Indications for PCV have not changed from previous recommendations. This report summarizes evidence considered for these recommendations and provides clinical guidance for use of PCV21.

Economic evaluation on meningococcal vaccination strategies among children under nine years of age in Zhejiang province, China.

Meningococcal vaccination in Chinese national immunization program (NIP) includes polysaccharide vaccine against Neisseria meningitidis serogroup A (MPV-A) and polysaccharide vaccine against Neisseria meningitidis serogroup A and C(MPV-AC). This study aimed to assess the cost-effectiveness of an alternative strategy using polysaccharide conjugate vaccine against Neisseria meningitidis serogroup A,C,W,Y(MCV-ACWY) and polysaccharide vaccine against Neisseria meningitidis serogroup A,C,W,Y(MPV-ACWY). From a societal perspective, we constructed a decision tree-Markov model to simulate the economic and health consequences of meningococcal disease in a 2023 birth cohort with the current meningococcal vaccination strategy and the alternative. Parameters of epidemiology, vaccine efficacy, cost, and utility were extracted from database and previous literatures. The sensitivity analysis was implemented to evaluate the robustness of the model. Compared to the current practice, the alternative strategy could avoid 513 meningococcal disease cases, 53 sequelae and 47 deaths. The ICER was estimated at $16899.81 /QALY, under the threshold of one time of the GDP per capita of Zhejiang province in 2023. The incidence of meningococcemia, the incidence of meningococcal meningitis, the case fatality of meningococcemia, the vaccine efficacy of MCV-ACWY and the price of MCV-ACWY would influence the cost-effectiveness of the meningococcal vaccination strategies. At the threshold, the probability of cost-effectiveness was 14.76% for the current strategy and 55.98% for the alternative strategy, respectively. The current meningococcal vaccination strategy had effectively prevented meningococcal disease at a low cost, but with limited serogroup coverage. Strategy using MCV-ACWY and MPV-ACWY could increase health benefits at a substantial cost at a cost-effective manner.

Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) in Preventing Community-Acquired Pneumonia in Adults: A Population-Based Cohort Study.

The aim was to assess the effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) in preventing CAP in adults. This was a population-based cohort study, followed up over 5 years (2015-2019), that included 47,768 persons aged ≥18 years assigned to three primary care centres. Data were retrospectively obtained from electronic medical records and databases. The vaccination effect was adjusted for potential confounders. Analyses were performed for the entire study population and for the ≥65 age subgroup. The annual incidence of CAP (per 103 adult inhabitants) was 3.29 overall, and 8.08 and 2.93 for vaccinated and non-vaccinated persons, respectively. The non-adjusted effect of PPV23 on CAP was evidenced by HR = 2.80 (95% CI: 2.32-3.37), and after adjusting for possible confounders, PPV23 showed no significant independent effect on CAP in the overall population (HR = 1.14; p = 0.277) or in persons aged ≥65 years (HR = 1.30; p = 0.051). No protective effect was observed in persons vaccinated <2 years previously (HR = 1.17; p = 0.514). PPV23 showed no effect in preventing CAP in adults aged ≥18 years or in the subgroup aged ≥65 years, even if vaccinated <2 years previously.

Protective Effects of 23-Valent Pneumococcal Polysaccharide Vaccination Against Mortality: The VENUS Study.

This retrospective matched cohort study investigated the protective effects of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against pneumonia mortality and all-cause mortality in Japanese adults aged ≥65 years. We analyzed claims data, vaccination records, and death certificate records between October 2016 and December 2019 from 55 509 PPSV23-vaccinated individuals and 55 509 unvaccinated individuals. Cox proportional hazards analyses were performed to calculate the adjusted hazard ratios (HRs) of PPSV23 vaccination for mortality. The results showed that PPSV23 vaccination was significantly associated with a reduction in all-cause mortality (adjusted HR, 0.52; P < .001) but not pneumonia mortality (adjusted HR, 0.70; P = .374).

Primary Immunodeficiency: Specific antibody deficiency with normal IgG.

Specific antibody deficiency (SAD) is a common primary immunodeficiency disorder that should be considered in older children and adults with recurrent and/or severe sinopulmonary infections. The diagnosis is characterized by inadequate antibody response to polysaccharide vaccine, specifically, pneumococcal, with normal responses to protein antigens and normal levels of serum immunoglobulins as well as immunoglobulin G (IgG) subclasses. The underlying mechanism for SAD is not completely elucidated. It is understood that young children have limited polysaccharide responsiveness, which develops with increased age. Due to this phenomenon, the consensus is that there is adequate immune maturity after age 2 years, which is the earliest for the SAD diagnosis to be established. There remains a lack of consensus on thresholds for polysaccharide nonresponse, and there are several commercial laboratories that measure a range of serotypes, with the recommendation for patients to have their diagnostic evaluation with serotype testing both before vaccination and after vaccination to be conducted by the same laboratory. Once a diagnosis has been made, the management of SAD is based on the clinical severity. Clinicians may consider prophylactic antibiotics as well as immunoglobulin replacement. These patients should be closely followed up, with the possibility of discontinuation of IgG replacement after 12 to 24 months. Children are more likely to demonstrate resolution of SAD than are adolescents and adults. Patients with SAD may also progress to a more severe immunodeficiency; therefore, continued monitoring remains a crucial principle of practice in the care of patients with SAD.

Comparative effectiveness of pneumococcal vaccination strategies to prevent invasive pneumococcal disease: a population-based cohort study at the veterans health administration in the United States

ObjectivesComparative effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13), 23-valent polysaccharide vaccine (PPSV23), and their combinations for adults in preventing invasive pneumococcal disease (IPD) has yet to be thoroughly investigated. We aimed to estimate the comparative effectiveness of preventing IPD, using population-based data from the Veterans Health Administration (VHA) in the United States. MethodsWe included all patients who were between 65 and 74 years, had established primary care within VHA between 2005 and 2021, and had not received any prior pneumococcal vaccination. We measured time-to-event from cohort enrolment to the onset of IPD, considering death a competing risk event, and used Cox regression models to estimate cause-specific hazards. PCV13 only, PPSV23 only, PCV13 after PPSV23, and PPSV23 after PCV13 were incorporated into models as time-dependent covariates. Patient demographics and comorbidities were also included in the model. ResultsA total of 3 044 067 patients were enrolled in the cohort, with 863 958 deaths (28.4%) and 1731 cases of IPD (0.06%) during the study period. The overall incidence rate of IPD in this population was 5.36 per 100 000 patient-years. A total of 921 070 patients (30.3%) received at least one dose of effective pneumococcal vaccine. In multivariate analysis adjusted for comorbidities, PCV13 alone was not associated with the reduced risk of IPD, whereas PPSV23 had protective association with IPD incidence (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.59–0.83). When combined, PCV13 followed by PPSV23 had a stronger protective association (aHR, 0.54; [0.36–0.83]) compared with PPSV23 followed by PCV13 (aHR, 0.73; [0.58–0.91]). Discussion: In this large cohort study at the VHA, the combination of PCV13 and PPSV23, particularly PCV13 followed by PPSV23, was associated with a lower risk of IPD, indicating additional benefits in combined vaccinations with potential importance in vaccination order. Further studies are needed to evaluate the effect of newer pneumococcal vaccines.

Immunogenicity and Safety of an Inactivated Quadrivalent Influenza Vaccine Administered Concomitantly with a 23-Valent Pneumococcal Polysaccharide Vaccine in Adults Aged 60 Years and Older.

The inactivated quadrivalent influenza vaccine (IIV4) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) have been administered for years and could be administered concomitantly if necessary. However, the immunogenicity and safety of the concomitant administration of these two vaccines have not been well documented, especially in the Chinese population. In this study, 480 participants aged 60 years and older were randomly assigned to the concomitant administration group (C group) or the separate administration group (S group) to receive IIV4 and PPSV23 either concomitantly or separately. Blood samples were collected before and 28 days after each vaccination. The antibodies against four influenza virus strains and twenty-three pneumococcus serotypes were tested. The results showed that the geometric mean titer (GMT) ratios (C group to S group) for the four influenza strains ranged from 0.72 to 0.95, with the lower limits of the 95% confidence intervals (CIs) ranging from 0.51 to 0.75, and the geometric mean concentration (GMC) ratios for the 23 pneumococcal serotypes ranged from 0.80 to 1.00, with the lower limits of 95% CIs ranging from 0.67 to 0.86. All values met the predefined criteria for non-inferiority. The incidence of adverse events was 0.63% in the C group and 1.56% in the S group. No serious adverse events were observed. In conclusion, the immunogenicity of the concomitant administration of IIV4 and PPSV23 was non-inferior to that of the separate administration, and the safety profile was favorable in adults aged 60 years and older in China.

Immunogenicity and safety of different combinations involving a third booster dose of SARS-CoV-2 inactivated vaccine, inactivated quadrivalent influenza vaccine, and 23-valent pneumococcal polysaccharide vaccine in adults aged ≥60 years: a phase 4, randomized, open-label study.

Concomitant administration of COVID-19, influenza, and pneumococcal vaccines could reduce the burden on healthcare systems. However, the immunogenicity and safety of various combinations of a third booster dose of SARS-CoV-2 inactivated vaccine (CoronaVac), inactivated quadrivalent influenza vaccine (IIV4), and 23-valent pneumococcal polysaccharide vaccine (PPV23), particularly in different age groups, is still unknown. A phase 4, randomized, open-label, controlled trial was conducted in Beijing, China. 636 healthy adults were divided into two age groups (18-59 and ≥60 years) and randomized equally into three groups: CoronaVac and IIV4 followed by PPV23; CoronaVac and PPV23 followed by IIV4; or CoronaVac followed by IIV4 and PPV23, with a 28-day interval between vaccinations. Immunogenicity was evaluated by measuring antibody titers, and safety was monitored. ClinicalTrials.gov Identifier: NCT05298800. Co-administration of a third dose of CoronaVac, IIV4, and PPV23 in any combination was safe. Among adults aged 18-59, co-administration with PPV23 maintained non-inferiority of antibody levels for CoronaVac and IIV4, despite a slight reduction in antibody responses. This reduction was not observed in participants ≥60 years. Furthermore, co-administration of IIV4 and PPV23 affected seroconversion rates for both vaccines. Co-administration of the third dose of SARS-CoV-2 inactivated vaccine with the influenza vaccine, followed by PPV23, may be optimal for adults aged 18-59. In adults ≥60, all vaccine combinations were immunogenic, suggesting a flexible vaccination approach. Since antibody measurements were taken 28 days post-vaccination, ongoing surveillance is essential to assess the longevity of the immune responses.

Secondary Immunodeficiency and Vaccine Response in Rheumatoid and Psoriatic Arthritis on Immunosuppressive Medicines.

Background Rheumatoid arthritis and psoriatic arthritis patients have dysregulated immune system parameters that may increase infection risk at baseline. In addition, treatment of these conditions with immunosuppressive medications may lead to the development of secondary immunodeficiency (SID). Our objective was to assess SID in a cohort on immunosuppressive medications. We hypothesized that SID is clinically detectable by assessing immune parameters and polysaccharide and protein-based vaccination responses. Methodology A prospective cohort study of 42 subjects on immunosuppressive medications was assessed. Analysis included immunoglobulin levels, lymphocyte subsets, and two-step response to diphtheria, tetanus, and 23-valent Streptococcus pneumoniae vaccinations. Exclusions included primary immunodeficiency, malignancy, pregnancy, neutropenia, immunoglobulin replacement, prior B-cell-depleting medication or chemotherapy, use of non-immunosuppressive medication, or recent use of glucocorticoids. Suboptimal vaccine response was defined as an abnormal response based on standard criteria for each vaccine. Results Low IgM levels (below 50 mg/dL) occurred in seven (17%) subjects and IgG (below 650 mg/dL) in three (7%) subjects. Impaired lymphocyte subsets were uncommon. In total, 33 (78%) subjects completed the two-step vaccination assessment. Overall, 29 of 33 (88%) subjects demonstrated suboptimal response to pneumococcal vaccination, 10 (30%) demonstrated suboptimal response to diphtheria, and four (12%) to tetanus. Two (6%) subjects demonstrated suboptimal response to all vaccinations. Finally, 31 (94%) subjects demonstrated suboptimal response to at least one vaccination. Conclusions SID may develop, is clinically detectable, and most notably demonstrated in suboptimal responses to polysaccharide vaccinations, especially against S. pneumoniae.

Novel manufacturing process of pneumococcal capsular polysaccharides using advanced sterilization methods.

Pneumococcal disease is caused by Streptococcus pneumoniae, including pneumonia, meningitis and sepsis. Capsular polysaccharides (CPSs) have been shown as effective antigens to stimulate protective immunity against pneumococcal disease. A major step in the production of pneumococcal vaccines is to prepare CPSs that meet strict quality standards in immunogenicity and safety. The major impurities come from bacterial proteins, nucleic acids and cell wall polysaccharides. Traditionally, the impurity level of refined CPSs is reduced by optimization of purification process. In this study, we investigated new aeration strategy and advanced sterilization methods by formaldehyde or β-propiolactone (BPL) to increase the amount of soluble polysaccharide in fermentation supernatant and to prevent bacterial lysis during inactivation. Furthermore, we developed a simplified process for the CPS purification, which involves ultrafiltration and diafiltration, followed by acid and alcohol precipitation, and finally diafiltration and lyophilization to obtain pure polysaccharide. The CPSs prepared from formaldehyde and BPL sterilization contained significantly lower level of residual impurities compared to the refined CPSs obtained from traditional deoxycholate sterilization. Finally, we showed that this novel approach of CPS preparation can be scaled up for polysaccharide vaccine production.