Post-primary Series Research Articles

Indirect Comparison of PCV20 Immunogenicity with PCV10 in Pediatric 3 + 1 and 2 + 1 Schedules

IntroductionThe 20-valent pneumococcal conjugate vaccine (PCV20) was licensed for prevention of pneumococcal disease in infants and children on the basis of immunogenicity compared with PCV13. We aimed to evaluate PCV20 immunogenicity compared with PCV10 (Synflorix; PhiD-CV) because both vaccines demonstrated lower immunogenicity than PCV13. Nevertheless, PCV10 was highly effective against vaccine-serotype pneumococcal disease in post-licensure studies. Since no study has directly compared PCV20 versus PCV10, we conducted an indirect comparison.MethodsWe conducted indirect comparisons for PCV20 versus PCV10 using data from published randomized control trials that directly compared these vaccines with PCV13 in 3 + 1 or 2 + 1 schedules. Serotype-specific immunoglobulin (Ig)G concentrations and opsonophagocytic activity (OPA) were assessed post-booster dose and post-primary series. First, geometric mean ratios (GMRs) were obtained for shared serotypes for each direct comparison against PCV13; we conducted a meta-analysis to generate pooled GMRs if data from multiple trials were available. Next, we indirectly compared relative GMRs of PCV20 versus PCV10 using PCV13 as the common comparator. In this descriptive analysis, GMRs > 1 favored PCV20 and GMR < 1 favored PCV10.ResultsMeta-analyses of PCV10 versus PCV13 data found that PCV10 was less immunogenic for most of the ten shared serotypes. When indirectly compared via PCV13, the relative immunogenicity of PCV20 versus PCV10 varied by serotype. Overall, IgG responses for the ten shared serotypes were similar for both 3 + 1 and 2 + 1 schedules, both post-primary series and post-booster dose. GMRs for both IgG and OPA were close to the line of equivalence, or spread between favoring PCV20 or PCV10.ConclusionsThe comparable immunogenicity of PCV20 versus PCV10 in 2 + 1 and 3 + 1 schedules suggests that PCV20 will have similar effectiveness for the ten serotypes included in both vaccines, including for direct protection during infancy and toddler age, while also expanding serotype coverage. Effectiveness for PCV20 needs to be confirmed in post-marketing studies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-025-01151-0.

Safety and immunogenicity of an mRNA-1273 vaccine booster in adolescents

ABSTRACT Safety, immunogenicity, and effectiveness of an mRNA-1273 50-μg booster were evaluated in adolescents (12–17 years), with and without pre-booster SARS-CoV-2 infection. Participants who had received the 2-dose mRNA-1273 100-µg primary series in the TeenCOVE trial (NCT04649151) were offered the mRNA-1273 50-μg booster. Primary objectives included safety and inference of effectiveness by establishing noninferiority of neutralizing antibody (nAb) responses after the booster compared with the nAb post-primary series of mRNA-1273 among young adults in COVE (NCT04470427). Binding antibody (bAb) responses against SARS-CoV-2 variants of interest and COVID-19 incidence after vaccination were also evaluated. Median boosting interval was 315 days. The mRNA-1273 booster was well-tolerated, with an acceptable safety profile. Relative to pre-booster, nAb geometric mean levels increased after the booster by 17.8-fold and 4.7-fold among pre-booster SARS-CoV-2–negative and –positive participants, respectively. Effectiveness was successfully inferred based on noninferiority of nAb levels from mRNA-1273 booster dose (Day 29) compared with nAb levels after mRNA-1273 primary series (Day 57) among young adults in COVE. Further, the booster increased bAb levels relative to pre-booster baseline against SARS-CoV-2 variants (alpha [B.1.1.7], beta [B.1.351], gamma [P.1], and delta [B.1.617.2]), regardless of pre-booster SARS-CoV-2 status. COVID-19 incidence (cases per 1000 person-months) was lower among boosted (0 cases) than non-boosted (95.766 cases) participants in January 2022, a peak period during the early omicron transmission. In summary, the mRNA-1273 50-μg booster induced robust nAb responses in previously vaccinated adolescents, regardless of SARS-CoV-2 serostatus. Effectiveness was successfully inferred and the booster was well-tolerated, with no new safety concerns identified.

Longitudinal Assessment of BNT162b2- and mRNA-1273-Induced Anti-SARS-CoV-2 Spike IgG Levels and Avidity Following Three Doses of Vaccination.

SARS-CoV-2 vaccination-induced protection against infection is likely to be affected by functional antibody features. To understand the kinetics of antibody responses in healthy individuals after primary series and third vaccine doses, sera from the recipients of the two licensed SARS-CoV-2 mRNA vaccines were assessed for circulating anti-SARS-CoV-2 spike IgG levels and avidity for up to 6 months post-primary series and 9 months after the third dose. Following primary series vaccination, anti-SARS-CoV-2 spike IgG levels declined from months 1 to 6, while avidity increased through month 6, irrespective of the vaccine received. The third dose of either vaccine increased anti-SARS-CoV-2 spike IgG levels and avidity and appeared to enhance antibody level persistence-generating a slower rate of decline in the 3 months following the third dose compared to the decline seen after the primary series alone. The third dose of both vaccines induced significant avidity increases 1 month after vaccination compared to the avidity response 6 months post-primary series vaccination (p ≤ 0.001). A significant difference in avidity responses between the two vaccines was observed 6 months post-third dose, where the BNT162b2 recipients had higher antibody avidity levels compared to the mRNA-1273 recipients (p = 0.020).

Longitudinal study of immunity to SARS-CoV2 in ocrelizumab-treated MS patients up to 2 years after COVID-19 vaccination.

(1) To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity. Sixty ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster. Binding anti-Spike antibody responses were assessed with multiplex bead-based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live-virus immunofluorescence-based microneutralization assay. Spike-specific cellular responses were assessed with IFNγ/IL-2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)-3 within T-cell receptors (Adaptive Biotechnologies). A linear mixed-effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses. The primary vaccination induced an 11- to 208-fold increase in binding and neutralizing antibody levels and a 3- to 4-fold increase in IFNγ/IL-2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3- to 5-fold increase in binding antibodies and 4- to 5-fold increase in IFNγ/IL-2, which were maintained for up to 1 year. Infections had a variable impact on immunity. Humoral and cellular benefits of COVID-19 vaccination in B-cell-depleted MS patients were sustained for up to 2 years when booster doses were administered.

Interim safety and immunogenicity of COVID-19 omicron BA.1 variant-containing vaccine in children in the USA: an open-label non-randomised phase 3 trial

Interim safety and immunogenicity of COVID-19 omicron BA.1 variant-containing vaccine in children in the USA: an open-label non-randomised phase 3 trial

Interruption of BTK inhibitor improves response to SARS-CoV-2 booster vaccination in patients with CLL

B-cell targeted therapies, including anti-CD20 monoclonal antibodies (mAb) and Bruton’s tyrosine kinase inhibitors (BTKi), further suppress antibody (Ab) response to vaccines in patients with chronic lymphocytic leukemia (CLL). We conducted a prospective cohort study of SARS-CoV-2 vaccination in 81 CLL patients receiving BTKi (n = 54), venetoclax (VEN, n = 9), or who were treatment naïve (TN, n = 18). Anti-spike Ab were detected in 53% of patients on BTKi post-primary series and 84% post-booster, 57% of patients on VEN post-primary series and 50% post-booster, and 67% of TN patients post-primary series and 87% post-booster. T-cell response to the primary series was independent of Ab response. At the time of booster, 12 patients interrupted BTKi (median 21 d, range 8–22) and 33 continued BTKi. Among patients with detectable Ab post-booster, those who interrupted BTKi (n = 10) had significantly higher Ab titers (median 7149 units/mL) compared with patients who continued BTKi (n = 27, median 2071 units/mL, p = .04).

Effect of COVID-19 vaccination on mortality by COVID-19 and on mortality by other causes, the Netherlands, January 2021–January 2022

Effect of COVID-19 vaccination on mortality by COVID-19 and on mortality by other causes, the Netherlands, January 2021–January 2022

A Phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of V114 compared with PCV13 in healthy infants (PNEU-PED-EU-1)

A Phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of V114 compared with PCV13 in healthy infants (PNEU-PED-EU-1)

Safety, tolerability, and immunogenicity of V114 pneumococcal vaccine compared with PCV13 in a 2+1 regimen in healthy infants: A phase III study (PNEU-PED-EU-2)

Safety, tolerability, and immunogenicity of V114 pneumococcal vaccine compared with PCV13 in a 2+1 regimen in healthy infants: A phase III study (PNEU-PED-EU-2)

P05 Safety, tolerability, and immunogenicity of V114 compared with PCV13 in preterm infants: a pooled subgroup analysis of four Phase III studies

Abstract Background Risk of invasive pneumococcal disease is 3-fold higher in preterm versus full-term infants, mainly due to underlying comorbidities and immunological immaturity. V114 is a 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 serotypes in 13-valent PCV (PCV13) plus two additional serotypes, 22F and 33F. A pooled subgroup analysis was performed in preterm infants (&amp;lt;37 weeks gestational age) enrolled in 4 paediatric Phase III studies evaluating the safety and immunogenicity of different 4-dose regimens of V114 or PCV13. Methods Safety was evaluated as the proportion of participants with AEs following each vaccination. Serotype-specific anti-pneumococcal IgG GMCs, IgG response rates, and OPA GMTs were measured at 30 days post-primary series (PPS; post-dose 3 [PD3]), pre-toddler dose, and 30 days post-toddler dose (PTD; post-dose 4 [PD4]). Results 174 and 180 participants received V114 and PCV13, respectively. Mean gestational age was 35.4 weeks (range: 27–37 weeks). Proportions of participants with any AE were comparable between vaccination groups following each vaccination; most solicited AEs were transient (≤3 days) and of mild-to-moderate intensity. V114-elicited IgG GMCs (Figure 1), IgG response rates, and OPA GMTs were generally comparable to PCV13 for the 13 shared serotypes and higher for serotypes 22F and 33F at 30 days PPS (PD3) and PTD (PD4). Conclusions In preterm infants, vaccination with V114 has an acceptable safety profile, is well tolerated, and induces comparable immune responses to PCV13 for the 13 shared serotypes and higher immune responses to V114 serotypes 22F and 33F. Study results support use of V114 in preterm infants.

Booster and Btki Interruption Improve Response to Sars-Cov-2 Vaccine in Patients with CLL

Booster and Btki Interruption Improve Response to Sars-Cov-2 Vaccine in Patients with CLL

Safety and immunogenicity of a hexavalent DTwP-IPV-HB-PRP∼T vaccine versus separate DTwP-HB-PRP∼T and IPV vaccines in healthy infants in India

Safety and immunogenicity of a hexavalent DTwP-IPV-HB-PRP∼T vaccine versus separate DTwP-HB-PRP∼T and IPV vaccines in healthy infants in India

Safety and immunogenicity of an inactivated eastern equine encephalitis virus vaccine

BackgroundEastern equine encephalitis virus (EEEV) is a mosquito borne alphavirus spread primarily in Atlantic and Gulf Coast regions of the United States. EEEV is the causative agent of a devastating meningoencephalitis syndrome, with approximately 30% mortality and significant morbidity. There is no licensed human vaccine against EEEV. An inactivated EEEV vaccine has been offered under investigational new drug (IND) protocols at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) since 1976. MethodsHealthy at-risk laboratory personnel received inactivated PE-6 strain EEEV (TSI-GSD 104) vaccine under two separate IND protocols. Protocol FY 99–11 (2002–2008) had a primary series consisting of doses on day 0, 7, and 28. Protocol FY 06–31 (2008–2016) utilized a primary series with doses on day 0 and 28, and month 6. Participants with an inadequate immune response, plaque reduction neutralization test with 80% cut-off (PRNT80) titer < 40, received booster vaccination. Volunteers with prior EEEV vaccination were eligible to enroll for booster doses based on annual titer evaluation. ResultsThe FY06-31 dosing schema resulted in significantly greater post-primary series immune response (PRNT80 ≥ 40) rates (84% vs 54%) and geometric mean titers (184.1 vs 39.4). The FY 06–31 dosing schema also resulted in significantly greater cumulative annual immune response rates from 1 to up to 7 years post vaccination (75% vs 59%) and geometric mean of titers (60.1 vs 43.0). The majority of probably or definitely related adverse events were mild and local; there were no probably or definitely related serious adverse events. ConclusionsInactivated PE-6 EEEV vaccine is safe and immunogenic in at-risk laboratory personnel. A prolonged primary series, with month 6 dose, significantly improved vaccine immunogenicity both post-primary series and longitudinally on annual titers. Despite decades of safe use under IND, full licensure is not planned due to manufacturing constraints, and ongoing development of alternatives.

Immunogenicity and safety of a hexavalent pediatric vaccine in HIV-exposed infected and uninfected infants in Republic of South Africa

ABSTRACT Human immunodeficiency virus (HIV)-exposed infants may be at increased risk of vaccine-preventable disease. This study was conducted as a post-licensure commitment in this population to evaluate the primary series, antibody persistence, and booster response to a licensed fully liquid hexavalent vaccine containing diphtheria (D), tetanus (T), acellular pertussis (aP), inactivated poliovirus (IPV), hepatitis B (HB), and Haemophilus influenzae type b antigens (PRP~T). This was a Phase III, open-label, randomized study conducted at a single center in the Republic of South Africa. The DTaP-IPV-HB-PRP~T vaccine was administered to HIV-exposed infected (Group A: N = 14) and HIV-exposed uninfected (Group B: N = 50) infants as a 6, 10, 14 week primary series with a toddler booster at 15–18 months of age. Immunogenicity of each antigen was measured using validated assays and vaccine reactogenicity was recorded using diary cards. The low number of HIV-exposed infected participants, due to widespread pre- and peri-natal retroviral treatment, meant that between-group comparisons should be treated with caution. In each group, primary series and booster immune seroprotection rates were strong, and pre-booster antibody persistence was good, although anti-HBs ≥10 mIU/mL in Group A was 78.6% post-primary series, 58.3% pre-booster, and 75.0% post-booster. There were no safety concerns. In conclusion, primary series and booster vaccination of the DTaP-IPV-HB-PRP~T vaccine were immunogenic and safe in HIV-exposed infected and uninfected infants. These results were comparable to historical data in healthy infants and toddlers.

Immunogenicity and safety of a DTaP-IPV/Hib pentavalent vaccine given as primary and booster vaccinations in healthy infants and toddlers in Japan

Immunogenicity and safety of a DTaP-IPV/Hib pentavalent vaccine given as primary and booster vaccinations in healthy infants and toddlers in Japan

Efficacy and Effectiveness of the PCV-10 and PCV-13 Vaccines Against Invasive Pneumococcal Disease.

Pneumococcal conjugate vaccines (PCVs) (pneumococcal 13-valent conjugate vaccine [PCV-13] and pneumococcal 10-valent conjugate vaccine [PCV-10]) are available for prevention of pneumococcal infections in children. To determine the vaccine effectiveness (VE) of PCV-13 and PCV-10 in preventing invasive pneumococcal disease (IPD) and acute otitis media (AOM) in children <5 years. Systematic searches of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Cochrane. Eligible studies examined the direct effectiveness and/or efficacy of PCV-10 and PCV-13 in reducing the incidence of disease in healthy children <5 years. Two reviewers independently conducted data extraction and methodologic quality assessment. Significant effectiveness against vaccine-type IPD in children ≤5 years was reported for ≥1 dose of PCV-13 in the 3 + 1 (86%-96%) and 2 + 1 schedule (67.2%-86%) and for PCV-10 for the 3 + 1 (72.8%-100%) and 2 + 1 schedules (92%-97%). In children <12 months of age, PCV-13 VE against serotype 19A post-primary series was significant for the 3 + 1 but not the 2 + 1 schedule. PCV-10 crossprotection against 19A was significant in children ≤5 years with ≥1 dose (82.2% and 71%). Neither PCVs were found effective against serotype 3. PCV-13 was effective against AOM (86%; 95% confidence interval [CI]: 61 to 94). PCV-10 was effective against clinically defined (26.9%; 95% CI: 5.9 to 43.3) and bacteriologically confirmed AOM (43.3%; 95% CI: 1.7 to 67.3). Because of the large heterogeneity in studies, a meta-analysis for pooled estimates was not done. Both PCVs afford protection against pneumococcal infections, with PCV-10 protecting against 19A IPD, but this VE has not been verified in the youngest age groups.

Comparison of hepatitis B surface antibody levels induced by the pentavalent DTwP-HB-Hib versus the hexavalent DTaP-HB-Hib-IPV vaccine, administered to infants at 2, 4, 6, and 18 months of age, following monovalent hepatitis B vaccination at birth

Comparison of hepatitis B surface antibody levels induced by the pentavalent DTwP-HB-Hib versus the hexavalent DTaP-HB-Hib-IPV vaccine, administered to infants at 2, 4, 6, and 18 months of age, following monovalent hepatitis B vaccination at birth

Evaluation of different infant vaccination schedules incorporating pneumococcal vaccination (The Vietnam Pneumococcal Project): protocol of a randomised controlled trial

IntroductionWHO recommends the use of pneumococcal conjugate vaccine (PCV) as a priority. However, there are many countries yet to introduce PCV, especially in Asia. This trial aims to evaluate different...

Second five-year follow-up after a booster vaccination against tick-borne encephalitis following different primary vaccination schedules demonstrates at least 10 years antibody persistence

BackgroundTick borne encephalitis (TBE) endemic zones are expanding. We previously evaluated long term persistence of antibody 5 years after the first booster immunization following different primary immunization schedules with the polygeline-free inactivated TBE vaccine (TBEvac) in adults and adolescents. Here, we report anti-TBE virus (TBEV) antibody persistence from 6 to 10 years post-booster administration. MethodsThis was a phase IV, open-label, single-center, second extension study (NCT01562444), conducted in Czechia. Healthy adults and adolescents ≥12 years who had received 3 different primary vaccination schedules (rapid, conventional and accelerated conventional) in the parent study and a booster dose before (12–18 months post-primary series completion) or at the beginning (3 years post-primary series completion) of the first extension study were screened and enrolled in this study. Blood samples were collected yearly and anti-TBEV antibody response was evaluated by neutralizing test (NT) antibody assays. Analysis was performed overall and per age strata: 15–49 years, ≥50 years, and ≥60 years. ResultsOf 206 screened individuals, 191 completed the study. Overall, 90–100% of participants in the all-screened set and ≥97% in the per-protocol set had the clinically meaningful threshold of protection (NT titers ≥10) across all timepoints, regardless of the primary vaccination schedule. Overall, antibody geometric mean titers (GMTs) varied from 134 to 343 in the all-screened set. Older age groups showed overall lower GMTs, although GMTs remained higher than NT titers ≥10 up to year 10 in all groups. ConclusionThis study showed long-term persistence of anti-TBEV NT antibodies for up to 10 years after the first booster dose of TBEvac in all age groups, regardless of the primary vaccination schedule.

A fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Turkish infants and toddlers

Background/aim: Immunogenicity and safety of a primary series of a fully liquid, hexavalent DTaP-IPV-HB-PRP-T vaccine given at 2, 3, and 4 months of age compared to licensed comparators and a DTaP-IPV-HB-PRP-T booster at 15?18 months were evaluated. Materials and methods: This was a Phase III, randomized, open-label trial. Primary series (no hepatitis B [HB] at birth) of DTaP-IPV-HB-PRP-T (N = 155) (group 1) or licensed control vaccines (DTaP-IPV//PRP-T and standalone HB: N = 155) (group 2) and DTaP-IPV-HB-PRP-T booster were administered. Noninferiority was evaluated 1 month postprimary series for anti-HB seroprotection (SP). All other analyses were descriptive. Safety was assessed from parental reports. Results: Postprimary series noninferiority of anti-HB ≥ 10 mIU/mL was demonstrated for the DTaP-IPV-HB-PRP-T vaccine (94.0%) compared to the licensed control (96.1%). Postprimary series primary SP and seroconversion (SC) rates were high and similar for both groups. Antibody persistence (prebooster) was high for each antigen and similar between groups except for HB, which was lower for DTaP-IPV-HB-PRP-T than for standalone HB. For each antigen except HB, DTaP-IPV-HB-PRP-T booster responses were high and similar in each group. Safety was good for primary and booster series and similar between groups. Conclusion: The DTaP-IPV-HB-PRP-T vaccine is immunogenic and safe when administered in a challenging primary series schedule without HB vaccination at birth.