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1.
PLoS Med ; 21(6): e1004375, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38829821

ABSTRACT

BACKGROUND: In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations. METHODS AND FINDINGS: In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size. CONCLUSIONS: In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01735084 and NCT01174849.


Subject(s)
Hearing Loss , Otitis Media , Pneumococcal Vaccines , Humans , Infant , Pneumococcal Vaccines/administration & dosage , Pneumococcal Vaccines/therapeutic use , Hearing Loss/epidemiology , Australia/epidemiology , Child, Preschool , Female , Male , Otitis Media/epidemiology , Otitis Media/prevention & control , Prevalence , Vaccines, Conjugate/administration & dosage , Pneumococcal Infections/prevention & control , Pneumococcal Infections/epidemiology , Immunization Schedule
2.
J Infect Dev Ctries ; 18(4): 579-586, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38728636

ABSTRACT

INTRODUCTION: Streptococcus pneumoniae cause a significant global health challenge. We aimed to determine nasopharyngeal carriage, serotypes distribution, and antimicrobial profile of pneumococci among the children of Aden. METHODOLOGY: A total of 385 children, aged 2-17 years, were included. Asymptomatic samples were randomly collected from children in selected schools and vaccination centers. Symptomatic samples were obtained from selected pediatric clinics. The nasopharyngeal swabs were tested for pneumococci using culture and real time polymerase chain reaction (RT-PCR). Serotyping was done with a pneumotest-latex kit and antimicrobial susceptibility was tested by disc diffusion and Epsilometer test. RESULTS: The total pneumococcal carriage was 44.4% and 57.1% by culture and RT-PCR, respectively. There was a statistically significant association between carriage rate and living in single room (OR = 7.9; p = 0.00001), sharing a sleeping space (OR = 15.1; p = 0.00001), and low monthly income (OR = 2.02; p = 0.007). The common serotypes were 19, 1, 4, 5, 2, and 23. The proportion of non-pneumococcal conjugate vaccine (non-PCV13) serotypes was 24%. Pneumococci were resistant to penicillin (96.5%), cefepime (15.8%), ceftriaxone (16.4%), and amoxicillin-clavulanate (0%). Erythromycin, azithromycin, and doxycycline had resistance rates of 48%, 31%, and 53.3%, respectively. CONCLUSIONS: A high pneumococcal carriage rate was observed in Yemeni children, particularly in low-income households and shared living conditions. There was significant penicillin resistance at meningitis breakpoint. Furthermore, non-PCV13 serotypes were gradually replacing PCV13 serotypes. The findings underscore the urgent need for enhanced surveillance and stewardship to improve vaccination and antibiotic policies in Yemen.


Subject(s)
Carrier State , Nasopharynx , Pneumococcal Infections , Pneumococcal Vaccines , Serogroup , Streptococcus pneumoniae , Vaccines, Conjugate , Humans , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/isolation & purification , Streptococcus pneumoniae/classification , Child , Child, Preschool , Cross-Sectional Studies , Yemen/epidemiology , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Infections/microbiology , Female , Male , Pneumococcal Vaccines/administration & dosage , Adolescent , Carrier State/epidemiology , Carrier State/microbiology , Nasopharynx/microbiology , Vaccines, Conjugate/administration & dosage , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Serotyping
3.
Expert Rev Vaccines ; 23(1): 546-560, 2024.
Article in English | MEDLINE | ID: mdl-38703180

ABSTRACT

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is used in the Japanese National Immunization Program for older adults and adults with increased risk for pneumococcal disease, however, disease incidence and associated burden remain high. We evaluated the cost-effectiveness of pneumococcal conjugate vaccines (PCVs) for adults aged 65 years and high-risk adults aged 60-64 years in Japan. RESEARCH DESIGN AND METHODS: Using a Markov model, we evaluated lifetime costs using societal and healthcare payer perspectives and estimated quality-adjusted life-years (QALYs), and number of prevented cases and deaths caused by invasive pneumococcal disease (IPD) and non-IPD. The base case analysis used a societal perspective. RESULTS: In comparison with PPSV23, the 20-valent PCV (PCV20) prevented 127 IPD cases 10,813 non-IPD cases (inpatients: 2,461, outpatients: 8,352) and 226 deaths, and gained more QALYs (+0.0015 per person) with less cost (-JPY22,513 per person). All sensitivity and scenario analyses including a payer perspective analysis indicated that the incremental cost-effectiveness ratios (ICERs) were below the cost-effectiveness threshold value in Japan (JPY5 million/QALY). CONCLUSIONS: PCV20 is both cost saving and more effective than PPSV23 for adults aged 65 years and high-risk adults aged 60-64 years in Japan.


Subject(s)
Cost-Benefit Analysis , Pneumococcal Infections , Pneumococcal Vaccines , Quality-Adjusted Life Years , Vaccines, Conjugate , Humans , Pneumococcal Vaccines/economics , Pneumococcal Vaccines/administration & dosage , Japan/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Infections/economics , Pneumococcal Infections/epidemiology , Middle Aged , Aged , Vaccines, Conjugate/economics , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/immunology , Male , Female , Markov Chains , Cost-Effectiveness Analysis
4.
Vaccine ; 42(16): 3555-3563, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38704263

ABSTRACT

BACKGROUND: A U.S. case-control study (2010-2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes. METHODS: We used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC's Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010-2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %). RESULTS: Among 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4-96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7-93.3 %), 50.2 % (28.4-80.5 %), and 93.8 % (69.8-98.8 %) against serotypes 19A, 3, and 19F, respectively. CONCLUSIONS: At least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance.


Subject(s)
Pneumococcal Infections , Pneumococcal Vaccines , Serogroup , Streptococcus pneumoniae , Humans , Pneumococcal Vaccines/administration & dosage , Pneumococcal Vaccines/immunology , Pneumococcal Infections/prevention & control , Pneumococcal Infections/epidemiology , United States/epidemiology , Child, Preschool , Infant , Female , Male , Streptococcus pneumoniae/immunology , Streptococcus pneumoniae/classification , Case-Control Studies , Vaccines, Conjugate/immunology , Vaccines, Conjugate/administration & dosage , Vaccine Efficacy/statistics & numerical data , Cohort Studies , Infant, Newborn , Vaccination/statistics & numerical data
5.
Hum Vaccin Immunother ; 20(1): 2333106, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38566502

ABSTRACT

Vaccine co-administration is a useful strategy for improving vaccine coverage and adherence. In Italy, an update to the national immunization program (NIP) in 2023 included recommendations for co-administration of pediatric vaccines, including the four-component vaccine for meningococcus B (4CMenB), pneumococcal conjugate vaccine (PCV), hexavalent vaccines, and oral rotavirus vaccines. Safety is a major concern when considering vaccine co-administration; therefore, a literature review of the available evidence on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines was performed. Of 763 publications screened, two studies were reviewed that reported safety data on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines in infants aged 0-24 months. Overall, these studies supported that there were no significant safety signals when co-administering 4CMenB with PCV, hexavalent/pentavalent, and rotavirus vaccines, compared with individual vaccination. This review provides key insights for healthcare professionals on the tolerability of co-administering 4CMenB with routine vaccines.


Subject(s)
Meningococcal Infections , Meningococcal Vaccines , Humans , Infant , Meningococcal Infections/prevention & control , Meningococcal Vaccines/administration & dosage , Neisseria meningitidis, Serogroup B , Rotavirus Vaccines/administration & dosage , Vaccination , Vaccines, Conjugate/administration & dosage , Infant, Newborn , Pneumococcal Vaccines/administration & dosage
6.
Vaccine ; 42(13): 3239-3246, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38609806

ABSTRACT

OBJECTIVE: To assess the health and economic outcomes of a PCV13 or PCV15 age-based (65 years-and-above) vaccination program in Switzerland. INTERVENTIONS: The three vaccination strategies examined were:Target population: All adults aged 65 years-and-above. Perspective(s): Switzerland health care payer. TIME HORIZON: 35 years. Discount rate: 3.0%. Costing year: 2023 Swiss Francs (CHF). STUDY DESIGN: A static Markov state-transition model. DATA SOURCES: Published literature and publicly available databases or reports. OUTCOME MEASURES: Pneumococcal diseases (PD) i.e., invasive pneumococcal diseases (IPD) and non-bacteremic pneumococcal pneumonia (NBPP); total quality-adjusted life-years (QALYs), total costs and incremental cost-effectiveness ratios (CHF/QALY gained). RESULTS: Using an assumed coverage of 60%, the PCV15 strategy prevented a substantially higher number of cases/deaths than the PCV13 strategy when compared to the No vaccination strategy (1,078 IPD; 21,155 NBPP; 493 deaths). The overall total QALYs were 10,364,620 (PCV15), 10,364,070 (PCV13), and 10,362,490 (no vaccination). The associated overall total costs were CHF 741,949,814 (PCV15), CHF 756,051,954 (PCV13) and CHF 698,329,579 (no vaccination). Thus, the PCV13 strategy was strongly dominated by the PCV15 strategy. The ICER of the PCV15 strategy (vs. no vaccination) was CHF 20,479/QALY gained. In two scenario analyses where the vaccine effectiveness for serotype 3 were reduced (75% to 39.3% for IPD; 45% to 23.6% for NBPP) and NBPP incidence was increased (from 1,346 to 1,636/100,000), the resulting ICERs were CHF 29,432 and CHF 13,700/QALY gained, respectively. The deterministic and probabilistic sensitivity analyses demonstrated the robustness of the qualitative results-the estimated ICERs for the PCV15 strategy (vs. No vaccination) were all below CHF 30,000/QALYs gained. CONCLUSIONS: These results demonstrate that using PCV15 among adults aged 65 years-and-above can prevent a substantial number of PD cases and deaths while remaining cost-effective over a range of inputs and scenarios.


Subject(s)
Cost-Benefit Analysis , Immunization Programs , Pneumococcal Infections , Pneumococcal Vaccines , Quality-Adjusted Life Years , Humans , Switzerland/epidemiology , Pneumococcal Vaccines/economics , Pneumococcal Vaccines/administration & dosage , Aged , Pneumococcal Infections/prevention & control , Pneumococcal Infections/economics , Pneumococcal Infections/epidemiology , Aged, 80 and over , Immunization Programs/economics , Male , Female , Vaccination/economics , Markov Chains , Streptococcus pneumoniae/immunology , Vaccines, Conjugate/economics , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/immunology , Pneumonia, Pneumococcal/prevention & control , Pneumonia, Pneumococcal/economics
7.
Vaccine ; 42(14): 3337-3345, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38637212

ABSTRACT

OBJECTIVES: We explored the role of metabolic hormones and the B-cell repertoire in the association between nutritional status and vaccine responses. METHODS: In this prospective cohort study, nested within a larger randomized open-label trial, 211 South African children received two doses of measles vaccine and two or three doses of pneumococcal conjugate vaccine (PCV). Metabolic markers (leptin, ghrelin and adiponectin) and distribution of B-cell subsets (n = 106) were assessed at 18 months of age. RESULTS: Children with a weight-for-height z-score (WHZ) ≤ -1 standard deviation (SD) at booster vaccination had a decreased mean serotype-specific PCV IgG response compared with those with WHZ > -1 and <+1 SD or WHZ ≥ +1 SD at 9 months post-booster (18 months of age). (Naive) pre-germinal center B-cells were associated with pneumococcal antibody decay between one to nine months post-booster. Predictive performance of elastic net models for the combined effect of B-cell subsets, metabolic hormones and nutritional status (in addition to age, sex, and randomization group) on measles and PCV vaccine response had an average area under the receiver operating curve of 0.9 and 0.7, respectively. CONCLUSIONS: The combined effect of B-cell subsets, metabolic hormones and nutritional status correlated well with the vaccination response for measles and most PCV serotypes. CLINICALTRIALS: gov registration of parent studies: NCT02943902 and NCT03330171.


Subject(s)
Antibodies, Bacterial , Measles Vaccine , Nutritional Status , Pneumococcal Vaccines , Humans , South Africa , Male , Female , Nutritional Status/immunology , Prospective Studies , Infant , Pneumococcal Vaccines/immunology , Pneumococcal Vaccines/administration & dosage , Measles Vaccine/immunology , Measles Vaccine/administration & dosage , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Leptin/blood , B-Lymphocytes/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Immunization, Secondary , Immunoglobulin G/blood , Ghrelin/immunology , B-Lymphocyte Subsets/immunology , Vaccines, Conjugate/immunology , Vaccines, Conjugate/administration & dosage , Vaccination
8.
Expert Rev Vaccines ; 23(1): 485-497, 2024.
Article in English | MEDLINE | ID: mdl-38682661

ABSTRACT

BACKGROUND: The Japanese National Immunization Program currently includes the pediatric 13 valent pneumococcal conjugate vaccine (PCV13) to prevent pneumococcal infections. We aimed to evaluate the cost-effectiveness of 20-valent PCV (PCV20) as a pediatric vaccine versus PCV13. METHODS: A decision-analytic Markov model was used to estimate expected costs, quality-adjusted life-years (QALYs), and prevented cases and deaths caused by invasive pneumococcal disease, pneumonia, and acute otitis media over a ten-year time horizon from the societal and healthcare payer perspectives. RESULTS: PCV20 was dominant, i.e. less costly and more effective, over PCV13 (gained 294,599 QALYs and reduced Japanese yen [JPY] 352.6 billion [2.6 billion United States dollars, USD] from the societal perspective and JPY 178.9 billion [USD 1.4 billion] from the payer perspective). Sensitivity and scenario analyses validated the robustness of the base scenario results. When comparing PCV20 with PCV13, the threshold analysis revealed an incremental cost-effectiveness ratio that was within the threshold value (JPY 5 million/QALY) at a maximum acquisition cost of JPY 74,033 [USD 563] (societal perspective) and JPY 67,758 [USD 515] (payer perspective). CONCLUSIONS: As a pediatric vaccine, PCV20 was dominant over PCV13 regardless of the study perspective.


Subject(s)
Cost-Benefit Analysis , Pneumococcal Infections , Pneumococcal Vaccines , Pneumococcal Vaccines/economics , Pneumococcal Vaccines/administration & dosage , Humans , Japan/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Infections/economics , Infant , Child, Preschool , Immunization Programs/economics , Vaccines, Conjugate/economics , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/immunology , Quality-Adjusted Life Years , Child , Vaccination/economics , Vaccination/methods , Male , Markov Chains , Female , Otitis Media/prevention & control , Otitis Media/economics , Adolescent , Cost-Effectiveness Analysis
9.
Vaccine ; 42(13): 3157-3165, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38637211

ABSTRACT

BACKGROUND: Introduction of pneumococcal conjugate vaccines (PCVs) reduced the number of cases of pneumococcal disease (PD). However, there is an increase in clinical and economic burden of PD from serotypes that are not part of the existing pneumococcal vaccines, particularly impacting pediatric and elder population. In addition, the regions where the PCV is not available, the disease burden remains high. In this study, immunogenicity and safety of the BE's 14-valent PCV (PNEUBEVAX 14™; BE-PCV-14) containing two additional epidemiologically important serotypes (22F and 33F) was evaluated in infants in comparison to licensed vaccine, Prevenar-13 (PCV-13). METHODS: This is a pivotal phase-3 single blind randomized active-controlled study conducted at 12 sites across India in 6-8 weeks old healthy infants at 6-10-14 weeks dosing schedule to assess immunogenic non-inferiority and safety of a candidate BE-PCV-14. In total, 1290 infants were equally randomized to receive either BE-PCV-14 or PCV-13. Solicited local reactions and systemic events, adverse events (AEs), serious AEs (SAEs), and medically attended AEs (MAAEs) were recorded. Immunogenicity was assessed by measuring anti-PnCPS (anti-pneumococcal capsular polysaccharide) IgG concentration and functional antibody titers through opsonophagocytic activity (OPA), one month after completing three dose schedule. Cross protection to serotype 6A offered by serotype 6B was also assessed in this study. FINDINGS: The safety profile of BE-PCV-14 was comparable to PCV-13 vaccine. Majority of reported AEs were mild in nature. No severe or serious AEs were reported in both the treatment groups. For the twelve common serotypes and for the additional serotypes (22F and 33F) in BE-PCV-14, NI criteria was demonstrated as defined by WHO TRS-977. Primary immunogenicity endpoint was met in terms of IgG immune responses for all 14 serotypesof BE-PCV-14. Moreover, a significant proportion of subjects (69%) seroconverted against serotype 6A, even though this antigen was not present in BE-PCV-14. This indicates that serotype 6B of BE-PCV-14 cross protects serotype 6A. BE-PCV-14 also elicited comparable serotype specific functional OPA immune responses to all the serotypes common to PCV-13. INTERPRETATIONS: BE-PCV-14 was found to be safe and induced robust and functional serotype specific immune responses to all 14 serotypes. It also elicited cross protective immune response against serotype 6B.These findings suggest that BE-PCV-14 can be safely administered to infants and achieve protection against pneumococcal disease caused by serotypes covered in the vaccine. The study was prospectively registered with clinical trial registry of India - CTRI/2020/02/023129.


Subject(s)
Antibodies, Bacterial , Pneumococcal Infections , Pneumococcal Vaccines , Streptococcus pneumoniae , Vaccines, Conjugate , Humans , Pneumococcal Vaccines/immunology , Pneumococcal Vaccines/adverse effects , Pneumococcal Vaccines/administration & dosage , Infant , India , Antibodies, Bacterial/blood , Male , Vaccines, Conjugate/immunology , Vaccines, Conjugate/adverse effects , Vaccines, Conjugate/administration & dosage , Female , Pneumococcal Infections/prevention & control , Pneumococcal Infections/immunology , Single-Blind Method , Streptococcus pneumoniae/immunology , Immunogenicity, Vaccine , Serogroup , Immunoglobulin G/blood
10.
Hum Vaccin Immunother ; 20(1): 2342630, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38687024

ABSTRACT

Since the introduction of Haemophilus Influenzae type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710-1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group - Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.


Vaccination against Haemophilus influenzae type b (Hib) is included in the majority of national immunization programs worldwide and has shown to be effective in preventing Hib disease. In Europe, different vaccines containing Hib components are marketed. We compared the immune response and safety of 2 of these (DTPa-HBV-IPV/Hib, Ih group) and DTaP5-HB-IPV-Hib, Va group) in infants and toddlers, when used in a 2 + 1 schedule, i.e. two primary vaccination doses (at 2 and 4 months of age of the infant), followed by one booster dose at the age of one year. One month after the booster vaccination, the antibody concentration ratio between both groups (Ih group/Va group) was 0.917 (95% CI: 0.710­1.185) showing the DTPa-HBV-IPV/Hib vaccine was non-inferior to the DTaP5-HB-IPV-Hib vaccine; the difference in percentage of participants (Ih group ­ Va group) with antibody concentrations above 5 µg/mL was -6.3% (95% CI: −14.1% to 1.5%), which did not meet the pre-defined criterion for non-inferiority. In the Ih group, the quality of antibodies produced was somewhat higher versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. The kinetics of the immune response are different between the 2 vaccines. Since both vaccines contain different additional components (conjugated proteins), a possible effect of concomitant (simultaneously administered) vaccines was studied. Further investigations to confirm our findings are needed.


Subject(s)
Antibodies, Bacterial , Haemophilus Vaccines , Haemophilus influenzae type b , Immunization Schedule , Polysaccharides , Vaccines, Combined , Vaccines, Conjugate , Humans , Haemophilus Vaccines/immunology , Haemophilus Vaccines/adverse effects , Haemophilus Vaccines/administration & dosage , Antibodies, Bacterial/blood , Infant , Female , Male , Single-Blind Method , Vaccines, Conjugate/immunology , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/adverse effects , Haemophilus influenzae type b/immunology , Vaccines, Combined/immunology , Vaccines, Combined/administration & dosage , Vaccines, Combined/adverse effects , Haemophilus Infections/prevention & control , Haemophilus Infections/immunology , Hepatitis B Vaccines/immunology , Hepatitis B Vaccines/administration & dosage , Hepatitis B Vaccines/adverse effects , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/adverse effects , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Diphtheria-Tetanus-Pertussis Vaccine/adverse effects , Child, Preschool , Immunogenicity, Vaccine , Europe
11.
J Adolesc Health ; 74(6): 1068-1077, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38430074

ABSTRACT

Invasive meningococcal disease (IMD) is a rare but serious illness, and adolescents and young adults in the United States are at increased risk. Here, we discuss US IMD history and how successful disease prevention through routine vaccination against the most common disease-causing serogroups (A, B, C, W, and Y) can inform future recommendations. Before the introduction of quadrivalent meningococcal conjugate (MenACWY) vaccines, most US cases of IMD were caused by serogroups B, C, and Y. After recommendation by the Advisory Committee on Immunization Practices for routine MenACWY vaccination of 11-12-year-olds in 2005, followed by a 2010 booster recommendation, MenCWY disease incidence declined dramatically, and vaccine coverage remains high. Two serogroup B (MenB) vaccines are licensed in the United States, but uptake is low compared with MenACWY vaccines, likely because Advisory Committee on Immunization Practices recommends MenB vaccination subject to shared clinical decision-making rather than routinely for all adolescents. The proportion of adolescent IMD caused by MenB has now increased. Pentavalent vaccines that protect against serogroups A, B, C, W, and Y may provide an optimal strategy for improving vaccination rates to ultimately reduce MenB incidence while maintaining the historically low rates of IMD caused by serogroups A, C, W, and Y.


Subject(s)
Meningococcal Infections , Meningococcal Vaccines , Humans , Meningococcal Vaccines/administration & dosage , United States , Adolescent , Meningococcal Infections/prevention & control , Vaccines, Conjugate/administration & dosage , Vaccination/statistics & numerical data , Neisseria meningitidis/immunology , Child
12.
Pediatr Infect Dis J ; 43(6): 587-595, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38456705

ABSTRACT

BACKGROUND: Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains. METHODS: This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PCV (PCV13) in healthy infants. Participants received 2 infant doses and a toddler dose of PCV20 or PCV13, with diphtheria-tetanus-acellular pertussis combination vaccine at all doses and measles, mumps, rubella and varicella vaccines at the toddler dose. Primary pneumococcal immunogenicity objectives were to demonstrate noninferiority (NI) of PCV20 to PCV13 for immunoglobulin G geometric mean concentrations after infant and toddler doses and percentages of participants with predefined serotype-specific immunoglobulin G concentrations after infant doses. Safety endpoints included local reactions, systemic events and adverse events. RESULTS: Overall, 1204 participants were vaccinated (PCV20, n = 601; PCV13, n = 603). One month after the toddler dose, 19/20 serotypes met NI for immunoglobulin G geometric mean concentrations; serotype 6B narrowly missed NI [PCV20/PCV13 geometric mean ratio: 0.57 (2-sided 95% confidence interval: 0.48-0.67); NI criterion: lower 2-sided 95% confidence interval >0.5]. Sixteen/twenty serotypes met NI for ≥1 primary objective after 2 infant doses. PCV20 induced robust opsonophagocytic activity, and boosting responses were observed for all vaccine serotypes, including those missing statistical NI. The safety/tolerability profile of PCV20 was like that of PCV13. CONCLUSIONS: PCV20 3-dose series in infants was safe and elicited robust immune responses. Based on these results and PCV13 experience, PCV20 3-dose series is expected to be protective for all 20 vaccine serotypes. NCT04546425.


Subject(s)
Antibodies, Bacterial , Pneumococcal Vaccines , Vaccines, Conjugate , Humans , Pneumococcal Vaccines/immunology , Pneumococcal Vaccines/administration & dosage , Pneumococcal Vaccines/adverse effects , Infant , Double-Blind Method , Male , Female , Antibodies, Bacterial/blood , Vaccines, Conjugate/immunology , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/adverse effects , Immunogenicity, Vaccine , Measles-Mumps-Rubella Vaccine/immunology , Measles-Mumps-Rubella Vaccine/administration & dosage , Measles-Mumps-Rubella Vaccine/adverse effects , Pneumococcal Infections/prevention & control , Pneumococcal Infections/immunology , Immunoglobulin G/blood , Chickenpox Vaccine/immunology , Chickenpox Vaccine/adverse effects , Chickenpox Vaccine/administration & dosage , Immunization Schedule , Streptococcus pneumoniae/immunology , Child, Preschool , Diphtheria-Tetanus-acellular Pertussis Vaccines/immunology , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Diphtheria-Tetanus-acellular Pertussis Vaccines/adverse effects , Vaccines, Combined
14.
Pediatr Infect Dis J ; 43(6): 574-581, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38502894

ABSTRACT

BACKGROUND: A 20-valent pneumococcal conjugate vaccine (PCV20), containing 13-valent PCV (PCV13) components and 7 additional polysaccharide conjugates, was developed to extend protection for pneumococcal disease. This phase 3 study assessed the safety and immunogenicity of PCV20 in children. METHODS: In this single-arm study, children (≥15 months-<18 years of age) received 1 dose of PCV20. Children <5 years of age had ≥3 prior doses of PCV13; children ≥5 years were recruited regardless of previous PCV receipt. Serotype-specific IgG concentrations and opsonophagocytic activity (OPA) titers were measured before and 1 month after PCV20. Local reactions and systemic events, adverse events (AEs), serious AEs, and newly diagnosed chronic medical conditions were collected. RESULTS: Of 839 enrolled participants, 831 (>99%) were vaccinated, and 819 (>97%) completed all study visits. Local reactions and systemic events were mostly mild to moderate in severity. No serious AEs were considered PCV20-related. IgG geometric mean fold rises (GMFRs) from before to 1 month after PCV20 ranged from 27.9-1847.7 (7 additional serotypes) and 2.9-44.9 (PCV13 serotypes) in children <5 years of age, and 10.5-187.7 (7 additional serotypes) and 4.3-127.9 (PCV13 serotypes) in children ≥5 years old. OPA GMFRs from before to 1 month after PCV20 ranged from 12.4-983.6 to 2.8-52.9 in children <5 years of age and from 11.5-499.0 to 5.3-147.9 in children ≥5 years of age. CONCLUSIONS: Among children ≥15 months through <18 years of age, PCV20 was well tolerated and induced robust responses to all 20 serotypes, supporting the use of PCV20 in children.


Subject(s)
Antibodies, Bacterial , Immunoglobulin G , Pneumococcal Infections , Pneumococcal Vaccines , Vaccines, Conjugate , Humans , Pneumococcal Vaccines/immunology , Pneumococcal Vaccines/adverse effects , Pneumococcal Vaccines/administration & dosage , Infant , Female , Male , Child, Preschool , Antibodies, Bacterial/blood , Adolescent , Child , Vaccines, Conjugate/immunology , Vaccines, Conjugate/adverse effects , Vaccines, Conjugate/administration & dosage , Pneumococcal Infections/prevention & control , Pneumococcal Infections/immunology , Immunoglobulin G/blood , Immunogenicity, Vaccine , Streptococcus pneumoniae/immunology , Serogroup
15.
Pediatr Infect Dis J ; 43(6): 596-603, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38535409

ABSTRACT

BACKGROUND: The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend pneumococcal disease protection beyond 13-valent PCV (PCV13). METHODS: This phase 3, double-blind study conducted in the United States/Puerto Rico evaluated PCV20 safety and immunogenicity. Healthy infants were randomized to receive a 4-dose series of PCV20 or PCV13 at 2, 4, 6 and 12-15 months old. Objectives included demonstrating noninferiority (NI) of PCV20 to PCV13 immunoglobulin G (IgG) geometric mean concentrations after doses 3 and 4 and percentages of participants with predefined IgG concentrations after dose 3, with 7 additional PCV20 serotypes compared with the lowest result among vaccine serotypes in the PCV13 group. Safety assessments included local reactions, systemic events, adverse events, serious adverse events and newly diagnosed chronic medical conditions. RESULTS: Overall, 1991 participants were vaccinated (PCV20, n = 1001; PCV13, n = 990). For IgG geometric mean concentrations 1 month after both doses 3 and 4, all 20 serotypes met NI criteria (geometric mean ratio lower 2-sided 95% confidence interval > 0.5). For percentages of participants with predefined IgG concentrations after dose 3, NI (percentage differences lower 2-sided 95% confidence interval > -10%) was met for 8/13 matched serotypes and 6/7 additional serotypes; 4 serotypes missed the statistical NI criterion by small margins. PCV20 also elicited functional and boosting responses to all 20 serotypes. The safety profile of PCV20 was similar to PCV13. CONCLUSION: A 4-dose series of PVC20 was well tolerated and elicited robust serotype-specific immune responses expected to help protect infants and young children against pneumococcal disease due to the 20 vaccine serotypes. Clinical trial registration: NCT04382326.


Subject(s)
Antibodies, Bacterial , Immunoglobulin G , Pneumococcal Infections , Pneumococcal Vaccines , Streptococcus pneumoniae , Vaccines, Conjugate , Humans , Pneumococcal Vaccines/immunology , Pneumococcal Vaccines/administration & dosage , Pneumococcal Vaccines/adverse effects , Infant , Double-Blind Method , Male , Female , Antibodies, Bacterial/blood , Pneumococcal Infections/prevention & control , Pneumococcal Infections/immunology , Immunoglobulin G/blood , Streptococcus pneumoniae/immunology , Vaccines, Conjugate/immunology , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/adverse effects , Immunogenicity, Vaccine , United States , Serogroup , Healthy Volunteers
17.
Lancet Infect Dis ; 24(5): 546-556, 2024 May.
Article in English | MEDLINE | ID: mdl-38310905

ABSTRACT

BACKGROUND: The UK transition from a 2 + 1 to a 1 + 1 infant immunisation schedule with the 13-valent pneumococcal conjugate vaccine (PCV13) on Jan 1, 2020, coincided with the start of the COVID-19 pandemic. We describe the epidemiology of invasive pneumococcal disease (IPD) in England over 6 financial years (April 1 to March 31) between 2017-18 and 2022-23. METHODS: We used prospective national surveillance data, including serotyping and whole-genome sequencing of invasive isolates, to analyse IPD trends in England by age and financial year. We compared breakthrough infections and vaccine failure rates in 2022-23 among children eligible for the 1 + 1 schedule with rates in cohorts of children eligible for the 2 + 1 schedule between 2017-18 and 2019-20. We assessed genomic changes over time by comparing Global Pneumococcal Sequencing Clusters and multilocus sequence types among PCV13 serotypes causing IPD. FINDINGS: There were 4598 laboratory-confirmed IPD cases in 2022-23, 3025 in 2021-22, 1240 in 2020-21, and 5316 in 2019-20. IPD incidence in 2022-23 was 14% lower than in 2019-20 (incidence rate ratio [IRR] 0·86, 95% CI 0·81-0·91; p<0·001). IPD incidence in 2022-23 compared with 2019-20 was 34% higher in children (aged <15 years) (378 cases vs 292 cases; IRR 1·34, 95% CI 1·08-1·68; p=0·009) and 17% lower in adults (aged 15 years and older; 4220 vs 5024; 0·83, 0·78-0·88; p<0·001). The proportion of PCV13-type IPD increased from 19·4% (95% CI 18·2-20·4; 957 of 4947) in 2019-20 to 29·7% (28·3-31·0; 1283 of 4326) in 2022-23, mainly due to serotype 3, but also serotypes 19F, 19A, and 4, alongside a decrease in non-PCV13 serotypes 8, 12F, and 9N. The increase in IPD incidence due to serotypes 3, 19A, and 19F was driven by clonal expansion of previously circulating strains, whereas serotype 4 expansion was driven by newer strains (ie, sequence types 801 and 15603). Breakthrough infections and vaccine failure rates were similar in children eligible for the 1 + 1 (1·08 per 100 000 person-years) and 2 + 1 (0·76 per 100 000 person-years; IRR 1·42, 95% CI 0·78-2·49; p=0·20) PCV13 schedules. INTERPRETATION: Overall, IPD incidence in England was lower in 2022-23, 2 years after removal of pandemic restrictions, than in 2019-20. Breakthrough and vaccine failure rates were not significantly different between children who received the 1 + 1 compared with the 2 + 1 PCV13 immunisation schedule. The post-pandemic increase in childhood IPD incidence and especially PCV13-type IPD will require close monitoring. FUNDING: None.


Subject(s)
Immunization Schedule , Pneumococcal Infections , Pneumococcal Vaccines , Streptococcus pneumoniae , Humans , Pneumococcal Vaccines/administration & dosage , Pneumococcal Infections/prevention & control , Pneumococcal Infections/epidemiology , England/epidemiology , Prospective Studies , Infant , Child, Preschool , Child , Streptococcus pneumoniae/classification , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/immunology , Adolescent , Male , Female , Adult , Incidence , Vaccines, Conjugate/administration & dosage , Serogroup , SARS-CoV-2/genetics , SARS-CoV-2/immunology , COVID-19/prevention & control , COVID-19/epidemiology , Middle Aged , Young Adult , Whole Genome Sequencing , Aged
18.
Infect Disord Drug Targets ; 24(5): e150124225640, 2024.
Article in English | MEDLINE | ID: mdl-38231056

ABSTRACT

OBJECTIVE: The purpose of this study was to find data proving the influence of the Haemophilus influenzae type b (Hib) conjugate vaccination on the frequency of invasive Hib illness. METHODOLOGY: A systematic literature search was conducted on the PubMed database to identify peerreviewed publications pertaining to the epidemiology of Haemophilus influenzae meningitis, both before and after the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines. The search query employed a combination of relevant keywords, including "invasive," "Haemophilus," "influenzae," "meningitis," and specific serotype b (Hib). Additionally, terms related to epidemiology, burden, risk factors, impact, Hib vaccine, Hib conjugate vaccine, combination vaccine, vaccine production, efficacy, immunisation coverage, surveillance, review, clinical aspects, outcomes, and various age groups (adults and children) were incorporated. RESULT: The search encompassed articles published till now. Subsequently, relevant research papers concerning Haemophilus influenzae meningitis were subjected to a comprehensive review and analysis. CONCLUSION: The Hib conjugate vaccination has shown to be extremely effective when administered to the entire population. However, changes to the immunisation protocol appear to be required in order to effectively manage invasive Hib illness.


Subject(s)
Haemophilus Vaccines , Haemophilus influenzae type b , Meningitis, Haemophilus , Vaccines, Conjugate , Adult , Child , Child, Preschool , Humans , Infant , Bacterial Capsules/immunology , Haemophilus Infections/prevention & control , Haemophilus Infections/epidemiology , Haemophilus Infections/microbiology , Haemophilus influenzae type b/immunology , Haemophilus Vaccines/administration & dosage , Haemophilus Vaccines/immunology , Meningitis, Haemophilus/prevention & control , Meningitis, Haemophilus/epidemiology , Meningitis, Haemophilus/microbiology , Vaccination , Vaccine Efficacy , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/immunology
19.
N Engl J Med ; 389(3): 215-227, 2023 Jul 20.
Article in English | MEDLINE | ID: mdl-37467497

ABSTRACT

BACKGROUND: Natural history studies have correlated serotype-specific anti-capsular polysaccharide (CPS) IgG in newborns with a reduced risk of group B streptococcal disease. A hexavalent CPS-cross-reactive material 197 glycoconjugate vaccine (GBS6) is being developed as a maternal vaccine to prevent invasive group B streptococcus in young infants. METHODS: In an ongoing phase 2, placebo-controlled trial involving pregnant women, we assessed the safety and immunogenicity of a single dose of various GBS6 formulations and analyzed maternally transferred anti-CPS antibodies. In a parallel seroepidemiologic study that was conducted in the same population, we assessed serotype-specific anti-CPS IgG concentrations that were associated with a reduced risk of invasive disease among newborns through 89 days of age to define putative protective thresholds. RESULTS: Naturally acquired anti-CPS IgG concentrations were associated with a reduced risk of disease among infants in the seroepidemiologic study. IgG thresholds that were determined to be associated with 75 to 95% reductions in the risk of disease were 0.184 to 0.827 µg per milliliter. No GBS6-associated safety signals were observed among the mothers or infants. The incidence of adverse events and of serious adverse events were similar across the trial groups for both mothers and infants; more local reactions were observed in the groups that received GBS6 containing aluminum phosphate. Among the infants, the most common serious adverse events were minor congenital anomalies (umbilical hernia and congenital dermal melanocytosis). GBS6 induced maternal antibody responses to all serotypes, with maternal-to-infant antibody ratios of approximately 0.4 to 1.3, depending on the dose. The percentage of infants with anti-CPS IgG concentrations above 0.184 µg per milliliter varied according to serotype and formulation, with 57 to 97% of the infants having a seroresponse to the most immunogenic formulation. CONCLUSIONS: GBS6 elicited anti-CPS antibodies against group B streptococcus in pregnant women that were transferred to infants at levels associated with a reduced risk of invasive group B streptococcal disease. (Funded by Pfizer and the Bill and Melinda Gates Foundation; C1091002 ClinicalTrials.gov number, NCT03765073.).


Subject(s)
Streptococcal Infections , Streptococcal Vaccines , Streptococcus agalactiae , Female , Humans , Infant , Infant, Newborn , Pregnancy , Antibodies, Bacterial , Immunoglobulin G , Seroepidemiologic Studies , Streptococcal Infections/epidemiology , Streptococcal Infections/immunology , Streptococcal Infections/prevention & control , Vaccines, Combined/administration & dosage , Vaccines, Combined/adverse effects , Vaccines, Combined/immunology , Vaccines, Combined/therapeutic use , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/adverse effects , Vaccines, Conjugate/immunology , Vaccines, Conjugate/therapeutic use , Streptococcal Vaccines/administration & dosage , Streptococcal Vaccines/adverse effects , Streptococcal Vaccines/immunology , Streptococcal Vaccines/therapeutic use , Immunity, Maternally-Acquired/immunology
20.
N Engl J Med ; 388(21): 1942-1955, 2023 May 25.
Article in English | MEDLINE | ID: mdl-37224196

ABSTRACT

BACKGROUND: An effective, affordable, multivalent meningococcal conjugate vaccine is needed to prevent epidemic meningitis in the African meningitis belt. Data on the safety and immunogenicity of NmCV-5, a pentavalent vaccine targeting the A, C, W, Y, and X serogroups, have been limited. METHODS: We conducted a phase 3, noninferiority trial involving healthy 2-to-29-year-olds in Mali and Gambia. Participants were randomly assigned in a 2:1 ratio to receive a single intramuscular dose of NmCV-5 or the quadrivalent vaccine MenACWY-D. Immunogenicity was assessed at day 28. The noninferiority of NmCV-5 to MenACWY-D was assessed on the basis of the difference in the percentage of participants with a seroresponse (defined as prespecified changes in titer; margin, lower limit of the 96% confidence interval [CI] above -10 percentage points) or geometric mean titer (GMT) ratios (margin, lower limit of the 98.98% CI >0.5). Serogroup X responses in the NmCV-5 group were compared with the lowest response among the MenACWY-D serogroups. Safety was also assessed. RESULTS: A total of 1800 participants received NmCV-5 or MenACWY-D. In the NmCV-5 group, the percentage of participants with a seroresponse ranged from 70.5% (95% CI, 67.8 to 73.2) for serogroup A to 98.5% (95% CI, 97.6 to 99.2) for serogroup W; the percentage with a serogroup X response was 97.2% (95% CI, 96.0 to 98.1). The overall difference between the two vaccines in seroresponse for the four shared serogroups ranged from 1.2 percentage points (96% CI, -0.3 to 3.1) for serogroup W to 20.5 percentage points (96% CI, 15.4 to 25.6) for serogroup A. The overall GMT ratios for the four shared serogroups ranged from 1.7 (98.98% CI, 1.5 to 1.9) for serogroup A to 2.8 (98.98% CI, 2.3 to 3.5) for serogroup C. The serogroup X component of the NmCV-5 vaccine generated seroresponses and GMTs that met the prespecified noninferiority criteria. The incidence of systemic adverse events was similar in the two groups (11.1% in the NmCV-5 group and 9.2% in the MenACWY-D group). CONCLUSIONS: For all four serotypes in common with the MenACWY-D vaccine, the NmCV-5 vaccine elicited immune responses that were noninferior to those elicited by the MenACWY-D vaccine. NmCV-5 also elicited immune responses to serogroup X. No safety concerns were evident. (Funded by the U.K. Foreign, Commonwealth, and Development Office and others; ClinicalTrials.gov number, NCT03964012.).


Subject(s)
Epidemics , Health Status , Meningitis , Meningococcal Vaccines , Vaccines, Conjugate , Humans , Gambia/epidemiology , Mali/epidemiology , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/adverse effects , Vaccines, Conjugate/therapeutic use , Meningococcal Vaccines/administration & dosage , Meningococcal Vaccines/adverse effects , Meningococcal Vaccines/therapeutic use , Child, Preschool , Child , Adolescent , Young Adult , Adult , Immunogenicity, Vaccine , Injections, Intramuscular , Meningitis/epidemiology , Meningitis/prevention & control , Epidemics/prevention & control
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