Explore the vast range of titles available.

Pneumococcal disease remains an important health priority despite successful implementation of pneumococcal conjugate vaccines (PCVs) in infant immunization programs, mainly due to the emergence of diseases caused by serotypes not included in licensed PCVs. A 15-valent pneumococcal conjugate vaccine (PCV-15) containing the 7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) included in licensed PCV-7 available at study initiation plus 8 additional serotypes (1, 3, 5, 6A, 7F, 19A, 22F, 33F) was developed and evaluated in healthy adults 18–45 years of age. Sixty subjects received one dose of PCV-15 or PCV-7. Injection-site and systemic adverse events (AEs) were collected for 14-days postvaccination and serious AEs were collected for 30-days postvaccination. Safety laboratory tests (hematology, chemistry, and urinalysis) were evaluated prior to vaccination and 14-days postvaccination. Serotype-specific IgG and opsonophagocytic killing activity (OPA) responses to 15 serotypes included in PCV-15 were measured immediately prior to vaccination and 30-days postvaccination. AE incidences were comparable between vaccine groups although numerically higher frequencies of erythema (33.3% versus 13.3%), swelling (50.0% versus 23.3%), and myalgia (63.3% versus 36.7%) were reported among PCV-15 versus PCV-7 recipients. Majority of AEs, irrespective of vaccine received, were transient and of mild-to-moderate intensity. No clinically significant differences were observed when comparing AE duration and severity. No laboratory abnormalities, vaccine-related SAEs or discontinuations from the study due to AEs were reported. IgG concentrations for the shared serotypes substantially increased postvaccination at comparable levels between recipients of PCV-15 and PCV-7. Substantial increases in antibody (IgG and OPA) responses to 8 serotypes unique to PCV-15 were observed in PCV-15 recipients. Slight increases to 2 serotypes unique to PCV-15, serotypes 6A and 19A, were also noted in PCV-7 recipients. PCV-15 displays an acceptable safety profile and induces IgG and OPA responses to all serotypes included in the vaccine.

The same pneumococcal conjugate vaccines (PCVs) have been used in adults and children in many settings. Differences in the epidemiology of pneumococcal disease between populations necessitates an adult-specific PCV. We aimed to assess the safety, tolerability, and immunogenicity of V116, an investigational 21-valent PCV designed for adults. This randomised, double-blind, active comparator controlled, international phase 3 trial enrolled adults with or without stable chronic medical conditions at 112 clinical sites in 11 countries or territories. Random assignment was performed using a central electronic interactive response technology system. Cohort 1 (≥50 years) was stratified by age (50–64, 65–74, 75–84, and ≥85 years) and randomised 1:1 to receive one intramuscular dose of V116, or the active comparator, PCV20. Cohort 2 (18–49 years) was randomised 2:1 to receive one intramuscular dose of V116 or PCV20. Pneumococcal serotype-specific opsonophagocytic activity (OPA) and IgG responses were measured before (day 1) and after vaccination (day 30). Four primary immunogenicity outcomes were assessed per-protocol. First, in cohort 1, non-inferiority of V116 to PCV20 was tested using serotype-specific OPA geometric mean titres (GMT) ratios for serotypes common to both vaccines; the lower bound of the 95% CI had to be greater than 0·5 for non-inferiority. Second, superiority of V116 to PCV20 was tested for OPA GMT ratios for the serotypes unique to V116; the lower bound of the 95% CI had to be greater than 2·0 for superiority. Third, superiority of V116 to PCV20 was evaluated by the proportions of participants with a four-fold or greater rise from day 1 to day 30 for serotypes unique to V116; the lower bound of the 95% CI of the differences in proportions (V116 – PCV20) had to be greater than 10% for superiority. Finally, in cohort 2, immunobridging was assessed for all 21 serotypes in V116 for adults aged 18–49 years to 50–64 years; the lower bound of the 95% CI for the OPA GMTs had to be greater than 0·5 for non-inferiority. The safety analysis included all randomly assigned participants who received study vaccine. The primary safety outcome was the proportion of participants with solicited injection site and solicited systemic adverse events until day 5 and vaccine-related serious adverse events up to 6 months after vaccination. This trial is registered at ClinicalTrials.gov (NCT05425732). Between July 13, and Nov 22, 2022, 2754 individuals were screened and 2663 participants were randomly assigned. 2656 individuals were vaccinated (1179 in V116 cohort 1; 1177 in PCV20 cohort 1; 200 in V116 cohort 2; and 100 in PCV20 cohort 2). V116 met non-inferiority criteria compared with PCV20 for the ten serotypes common to both vaccines at day 30 in cohort 1 (p<0·0001 for each common serotype). V116 met superiority criteria compared with PCV20 in cohort 1 for ten of the 11 serotypes unique to V116 at day 30 (OPA GMT ratio: p<0·0001 for all unique serotypes except 15C, which was p=0·41; four-fold or greater rise in OPA from day 1–30: p<0·0001 for all serotypes except 15C, which was p=0·67). Immune responses in V116 participants aged 18–49 years were non-inferior compared with V116 participants aged 50–64 years for all V116 serotypes (p<0·0001 for all V116 serotypes). In cohort 1, 685 (58·2%) of participants in V116, and 778 (66·2%) of participants in PCV20 reported one or more adverse event. In cohort 2, 164 (82·0%) participants in V116 and 79 participants (79·0%) in PCV20 reported one or more adverse event. Six deaths were reported, all in cohort 1, none of which were considered vaccine-related (in V116: one due to sepsis, one due to cerebrovascular accident, one due to myocardial infarction, and one due to hepatic cirrhosis and hepatic encephalopathy; in PCV20: one due to cardiac arrest and one due to abdominal abscess). There were no vaccine-related serious adverse events. V116 was non-inferior to PCV20 for the ten serotypes common to both vaccines and superior to PCV20 for all serotypes unique to V116, except for 15C. Immune responses successfully immunobridged between younger and older adults for all serotypes in V116. V116 was generally well tolerated with safety profile similar to PCV20. Merck Sharp & Dohme, subsidiary of Merck & Co, Rahway, NJ, USA (MSD).

Pneumococcal conjugate vaccines (PCVs) are generally administered in infant schedules with other vaccines. Here, we describe the safety and immunogenicity of routinely recommended pediatric vaccines given with 20-valent-PCV (PCV20). Two phase 3, double-blind, randomized trials evaluated the safety, tolerability, and immunogenicity of PCV20 in infants with concomitant pediatric vaccines. The studies examined a 4-dose series (Study B7471011/NCT04382326; N = 1997) and a 3-dose series (Study B7471012/NCT04546425; N = 1207). Concomitant vaccinations included a combination vaccine (diphtheria, tetanus, acellular pertussis [DTaP] with hepatitis B and poliovirus antigens (DTaP-HBV-IPV) and Haemophilus influenzae type b vaccine [Hib]) in Study B7471011 or combined vaccine (DTaP, hepatitis B, poliovirus, and Hib antigens [DTaP-HBV-IPV/Hib]) in Study B7471012. Measles, mumps, rubella (MMR) and varicella vaccines were given concomitantly with the toddler dose in both studies. Immunogenicity objectives were to demonstrate noninferiority of immune responses to concomitant vaccine antigens for concomitant vaccines given with PCV20 to those given with 13-valent PCV (PCV13). Safety endpoints included systemic events and adverse events (AEs). Noninferiority was met for the primary objectives of percentage of participants with prespecified antibody levels to the DTaP-HBV-IPV and Hib 1 month after the third infant dose (Study B7471011) and 1 month after the toddler dose of DTaP-HBV-IPV/Hib (Study B7471012) in the PCV20 group compared with the PCV13 group. Noninferiority was also met for the geometric mean antibody levels to MMR and varicella vaccines 1 month after the toddler dose in both studies. Systemic event frequencies were similar in the PCV20 and PCV13 groups in both studies, with severity mostly reported as mild or moderate. Frequencies of reported AEs were similar between the PCV20 and PCV13 groups. Immune responses to routine pediatric vaccines given with PCV20 were noninferior to those when given with PCV13. PCV20 may be safely administered with other routine pediatric vaccines. (NCT04382326; NCT04546425). •Two phase 3, double-blind, randomized trials evaluated PCV20 in infants.•The studies included concomitant administration of routine pediatric vaccines.•Immune responses to these concomitant pediatric vaccines were evaluated.•Responses to concomitant vaccines were noninferior with PCV20 to those with PCV13.•PCV20 may be safely administered with other routine pediatric vaccines.

•Limited evidence suggests that PCVs impact vaccine-type carriage density.•This double-blind PCV study suggests no impact on vaccine-type carriage density.•PCV13 may affect carriage by reducing carrier number but not vaccine-type density.•Carriage density may not impact herd effects. In addition to reducing vaccine-type nasopharyngeal carriage rates, pneumococcal conjugate vaccines (PCVs) may decrease carriage density in vaccinated individuals still carrying vaccine serotypes. However, reduction of carriage density has not been systematically studied. This study compared the effect of PCV13 versus PCV7 on carriage density of the serotypes in PCV13 that are not included in PCV7. This randomized, double-blind study was conducted in southern Israel and included Jewish and Bedouin subjects. Per protocol, 881 and 873 infants received PCV13 and PCV7, respectively, at ages 2, 4, 6, and 12months. Nasopharyngeal cultures at ages 7, 12, 13, 18, and 24months were plated using the 4-quadrant semiquantitative method and graded 0 (negative) to 4 (growth in all plate quadrants). In this post hoc analysis, the least squares means of cumulative colonization densities per serotype and serotype combination of the total population and each ethnic subpopulation in each vaccine group were calculated, and differences between vaccine groups derived from a linear model. PCV13-vaccinated children still carrying the 6 additional PCV13 serotypes unique to PCV13 showed no significant differences in carriage density compared with the PCV7-vaccinated control group. No differences in carriage density were shown between Jewish and Bedouin subpopulations despite higher carriage rates among Bedouin subjects. Although PCV13 vaccination reduces vaccine-type carriage compared with PCV7 vaccination by reducing nasopharyngeal acquisition of the additional PCV13 serotypes as previously reported, the current study lacks evidence of a decrease in carriage density of these serotypes when acquired in vaccinated children. Despite the lack of effect on carriage density observed, surveillance data suggest a dramatic decrease in disease rates after PCV implementation. Thus, the current analysis suggests that PCV’s impact on carriage density has minimal or no impact on vaccine success. (www.ClinicalTrials.gov: NCT00508742)

Pneumococcal conjugate vaccines are an important but costly part of childhood vaccination. This trial assessed immunogenicity of fractional-dose regimens — a key consideration as countries transition out of Gavi support.

•Increase in GMCs of serotype-specific IgG levels in PCV7 group.•Increase in GMTs of OIs of serotype-specific IgG levels in PCV7 group.•Our study confirmed the safety of both PCV7 and PPV23 vaccines in elderly people.•PCV7 displayed superior immunogenicity than PPV23 in 4/7 serotypes included in PCV7. An open-labeled randomized study was conducted to compare the immunogenicity and safety of polysaccharide (PPV23) or protein-conjugated pneumococcal vaccine (PCV7) among the elderly aged 80 years or older. A total of 105 nursing home residents were enrolled in this study. We analyzed the geometric mean concentration (GMC) of serotype-specific immunoglobulin G (IgG) and the geometric mean titer (GMT) of the opsonization index (OI) for serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. The GMCs of serotype-specific IgG and the GMTs of the OI significantly increased one month after vaccination in both groups for all seven serotypes evaluated. In the PCV7 group, study subjects with serotypes 4, 9V, 18C, and 23F exhibited statistically significant elevations in both serotype-specific IgGs and OIs compared to those of the PPV23 group. Both vaccines were tolerated without any severe adverse events, and no differences in systemic adverse events were observed between the two groups, although adverse reactions such as redness and localized swelling were more common in the PCV7 group. Our data demonstrated that the GMCs of serotype-specific IgG and the GMTs of the OI were higher in the PCV7 group compared to those in the PPV23 group. Our study also confirmed the safety of both the PCV7 and PPV23 vaccines in elderly people aged 80 years or older.

Pneumococcal disease (PD) prevention remains an unmet medical need in older adults. V116 is an adult-specific, 21-valent pneumococcal conjugate vaccine (PCV) specifically designed to provide protection against pneumococcal serotypes associated with a large proportion of residual invasive pneumococcal disease (IPD). This phase 3 study evaluated the safety, tolerability, and immunogenicity of V116 compared with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in Japanese older adults (NCT05633992). In this phase 3, randomized, double-blind, active comparator-controlled study, 450 vaccine-naïve adults ≥65 years of age were randomized 1:1 to receive a single dose of V116 or PPSV23. Primary immunogenicity objectives were to assess opsonophagocytic activity (OPA) and demonstrate: i) non-inferiority for V116 versus PPSV23 across 12 common serotypes, and cross-reactive serotype 15B in V116, based on geometric mean titers (GMTs) at Day 30; and ii) superiority for nine serotypes unique to V116 based on the proportions of participants exhibiting ≥4 fold rises in serotype-specific OPA responses between baseline and Day 30 (excluding serotype 15C) or based on GMTs at Day 30 (serotype 15C only). The primary safety outcome measured the proportion of participants with adverse events (AEs). V116 was non-inferior compared with PPSV23 for the 12 common serotypes and for the cross-reactive serotype 15B. V116 was superior compared with PPSV23 for the nine unique serotypes (including serotype 15C). The proportion of participants with AEs was comparable between V116 and PPSV23, and there were no vaccine-related serious AEs or deaths. In vaccine-naïve Japanese adults ≥65 years of age, V116 is well tolerated, with a safety profile comparable to PPSV23, and elicits immune responses to all V116 serotypes and the cross-reactive serotype 15B. V116 has the potential to broaden protection against PD in Japan through the inclusion of serotypes responsible for the majority of residual PD in adults. •IPD burden is highest in adults ≥65 years of age; this group accounts for 29 % of Japan's population.•Residual PD remains an unmet medical need, partly caused by non-vaccine-type serotypes.•Serotypes in V116 are responsible for ∼80 % of residual IPD in individuals ≥15 years of age in Japan.•V116 has the potential to broaden protection against residual PD in adults.

•All 3 doses of VAX-24 were well tolerated, with a safety profile similar to PCV20.•All treatment arms resulted in robust increases in OPA GMTs and IgG GMCs.•VAX-24 achieved higher serotype valency and enhanced immune responses versus PCV20. Despite current polysaccharide and conjugate vaccine use, pneumococcal diseases remain prevalent in older adults. VAX-24 is a 24-valent pneumococcal conjugate vaccine (PCV) containing eCRM, a proprietary carrier protein with non-native amino acids (para-azidomethyl-L-phenylalanine) that undergo site-specific conjugation to pneumococcal polysaccharides that have been activated with a small-molecule linker (dibenzocyclooctyne). Site-specific conjugation utilizing click chemistry enables consistent exposure of T-cell epitopes, reduction in carrier protein to pneumococcal polysaccharide ratio, and enhances manufacturing process consistency to improve PCVs by increasing serotype coverage while minimizing carrier suppression. Healthy adults aged 65 or older were randomized in a 1:1:1:1 ratio to receive a single injection of VAX-24 at 1 of 3 dose levels (1.1, 2.2, or a mixed dose of 2.2 or 4.4 mcg) or Prevnar 20® (PCV20) in a phase 2, blinded study. Primary outcome measures were solicited local and systemic events within 7 days post-vaccination, unsolicited adverse events (AEs) within 1 month, and serious AEs, medically attended AEs, or new onset of chronic disease within 6 months of vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) were measured pre-vaccination and at 1 month post-vaccination. Of 207 participants enrolled, 200 completed the trial. Safety profiles were comparable across the three VAX-24 doses and PCV20. Robust OPA and IgG immune responses were seen for all 24 serotypes. On average, immune responses to VAX-24 2.2 mcg dose were similar or higher compared to PCV20. In adults ≥ 65 years, VAX-24 had a safety profile similar to PCV20 through six months post-vaccination and induced robust OPA and IgG responses to all 24 serotypes, supporting prior data showing that site-specific conjugation allows for increased serotype coverage with similar or higher immune response vs other PCVs. The outcome of this phase 2 study further supports use of VAX-24 2.2 mcg dose in phase 3 trials. Clinicaltrials.gov: NCT05297578.

This phase 3, randomized, partially double-blind study investigated the safety, tolerability, and immunogenicity of 20-valent pneumococcal conjugate vaccine (PCV20) in healthy toddlers ≥12–<24 months of age who had previously received 2 infant doses of 13-valent PCV (PCV13). Participants were randomized to receive 1 or 2 doses of PCV20 (the second dose was administered 56–70 days after the first dose), or 1 dose of PCV13. The primary pneumococcal immunogenicity endpoint was the percentages of participants with predefined serotype-specific immunoglobulin G (IgG) concentrations (≥0.35 μg/mL) for the 7 additional serotypes 1 month after the last vaccination. Percentages of participants with predefined IgG concentrations for the 13 matched serotypes, IgG geometric mean concentrations, and opsonophagocytic activity (OPA) geometric mean titers were also evaluated for all 20 vaccine serotypes. Safety endpoints included local reactions, systemic events, adverse events, and serious adverse events. Overall, 356 participants were randomized (2-dose PCV20, n = 121; 1-dose PCV20, n = 118; PCV13, n = 117). One month after 1 PCV20 dose, ≥75.9 % of participants had IgG concentrations ≥0.35 μg/mL for all 7 additional serotypes, except serotype 12F (54.6 %). After 2 PCV20 doses, the percentage of participants with IgG concentrations ≥0.35 μg/mL for the 7 additional serotypes was ≥91.2 %. PCV20 elicited IgG and OPA responses for all 20 serotypes including serotype 12F. IgG distributions were well differentiated and substantially higher in PCV20 groups than the PCV13 group for the 7 additional serotypes, and generally similar between all groups for the 13 matched serotypes. In conclusion, a single toddler dose of PCV20 after 2 infant PCV13 doses elicited immune responses expected to help provide protection against the 7 additional serotypes and to provide similar protection against the 13 matched serotypes as PCV13. These data support a transition from PCV13 to PCV20 at the toddler dose. The safety and tolerability profile of PCV20 was similar to PCV13. Trial registration:Clinicaltrials.gov, NCT05408429. •PCV20 safety, tolerability, and immunogenicity in healthy toddlers was investigated.•Participants had previously received 2 infant doses of PCV13.•PCV20 single toddler dose expected to help protect against 7 additional serotypes.•PCV20 expected to provide similar protection as PCV13 against 13 matched serotypes.•The safety/tolerability profile of PCV20 toddler doses was similar to PCV13.

Disease caused by Streptococcus pneumoniae is associated with considerable morbidity and mortality in adults. V116 is an approved 21-valent pneumococcal conjugate vaccine with a serotype composition designed to address the majority of residual pneumococcal disease in adults. This phase 3 study evaluated the safety, tolerability, and immunogenicity of V116 when administered concomitantly with quadrivalent influenza vaccine (QIV) in adults. A total of 1080 healthy adults ≥ 50 years of age were randomized 1:1 to receive QIV and V116 concomitantly (n = 540) or QIV followed by V116 30 days later (n = 540). Immunogenicity was evaluated at 30 days postvaccination using opsonophagocytic activity (OPA) geometric mean titers (GMTs) and immunoglobulin G (IgG) geometric mean concentrations (GMCs) for V116, and hemagglutination inhibition (HAI) GMTs for QIV. For V116, the statistical criterion for noninferiority between groups required the lower bound of the 2-sided 95 % confidence interval of the OPA GMT ratio (concomitant/sequential groups) to be > 0.5. For QIV, the statistical criterion for noninferiority required the lower bound of the 2-sided 95 % CI of the HAI GMT ratio (concomitant/sequential groups) to be >0.67. Safety was evaluated by the proportion of participants with adverse events (AEs). The concomitant group met the primary noninferiority immunogenicity endpoints for 20 of 21 serotypes in V116 and for 3 of 4 influenza strains in QIV; noninferiority criteria were narrowly missed for serotype 23B and influenza H3N2. IgG GMCs at 30 days postvaccination were generally comparable between groups for all V116 serotypes. The proportions of participants with injection-site, systemic, vaccine-related, and serious AEs were generally comparable between groups. In adults ≥ 50 years of age, V116 is well tolerated and immunogenic when given concomitantly with QIV. Study results support use of V116 with QIV.