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Background MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated approximately 50% efficacy against human cytomegalovirus (HCMV) acquisition in multiple clinical trials, suggesting that efforts to improve this vaccine design might yield a vaccine suitable for licensure. Methods A messenger RNA (mRNA)–based vaccine candidate encoding HCMV gB and pentameric complex (PC), mRNA-1647, is currently in late-stage efficacy trials. However, its immunogenicity has not been compared to the partially effective gB/MF59 vaccine. We assessed neutralizing and Fc-mediated immunoglobulin G (IgG) effector antibody responses induced by mRNA-1647 in both HCMV-seropositive and -seronegative vaccinees from a first-in-human clinical trial through 1 year following third vaccination using a systems serology approach. Furthermore, we compared peak anti-gB antibody responses in seronegative mRNA-1647 vaccinees to that of seronegative gB/MF59 vaccine recipients. Results mRNA-1647 vaccination elicited and boosted HCMV-specific IgG responses in seronegative and seropositive vaccinees, respectively, including neutralizing and Fc-mediated effector antibody responses. gB-specific IgG responses were lower than PC-specific IgG responses. gB-specific IgG and antibody-dependent cellular phagocytosis responses were lower than those elicited by gB/MF59. However, mRNA-1647 elicited higher neutralization and antibody-dependent cellular cytotoxicity (ADCC) responses. Conclusions Overall, mRNA-1647 vaccination induced polyfunctional and durable HCMV-specific antibody responses, with lower gB-specific IgG responses but higher neutralization and ADCC responses compared to the gB/MF59 vaccine. Clinical Trials Registration NCT03382405 (mRNA-1647) and NCT00133497 (gB/MF59). [ABSTRACT FROM AUTHOR]

Background With the future epidemiology and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uncertain, the use of safe and effective coronavirus disease 2019 (COVID-19) vaccines in pediatric populations remains important. Methods We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating the safety and immunogenicity of a variant-adapted bivalent COVID-19 vaccine encoding ancestral and Omicron BA.4/BA.5 spike proteins (bivalent BNT162b2). The open-label groups presented here evaluate dose 4 with bivalent BNT162b2 in 6-month- to <12-year-olds who previously received three original (monovalent) BNT162b2 doses. In 6-month- to <5-year-olds, primary immunogenicity objectives were to demonstrate superiority (neutralizing titer) and noninferiority (seroresponse rate) to Omicron BA.4/BA.5 and noninferiority (neutralizing titer and seroresponse rate) to SARS-CoV-2 ancestral strains in participants who received bivalent BNT162b2 dose 4 compared with a matched group who received three doses of original BNT162b2 in the pivotal pediatric study (NCT04816643). In 5- to <12-year-olds, primary immunogenicity comparisons were descriptive. Reactogenicity and safety following vaccination were evaluated. Results In 6-month- to <5-year-olds, dose 4 with bivalent BNT162b2 met predefined immunogenicity superiority and noninferiority criteria against Omicron BA.4/BA.5 and ancestral strains when compared with dose 3 of original BNT162b2. In 5- to <12-year-olds, bivalent BNT162b2 induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers comparable with dose 3 of original BNT162b2. The safety profile for dose 4 of bivalent BNT162b2 given as dose 4 was consistent with that of original BNT162b2 in 6-month- to <12-year-olds. Reactogenicity events were generally mild to moderate. No adverse events led to discontinuation. Conclusions These safety and immunogenicity data support a favorable benefit-risk profile for a variant-adapted BNT162b2 in children <12 years old. [ABSTRACT FROM AUTHOR]

Introduction A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs. Methods Healthy adults (n = 180), ages 19–50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 dosages (3.75 or 15 μg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition and neutralizing antibody titers were assessed. Results Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest hemagglutination inhibition geometric mean titer (95% confidence interval) observed against the 2017 A(H7N9) strain was 133.4 (83.6–212.6) among participants who received homologous, adjuvanted 3.75 µg + AS03/2017 doses with delayed boost interval. Conclusions Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. Clinical Trials Registration. NCT03589807. [ABSTRACT FROM AUTHOR]

We compared the serologic responses of 1 dose versus 2 doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A 2-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost. [ABSTRACT FROM AUTHOR]

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wild-type spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines. [ABSTRACT FROM AUTHOR]

Background We evaluated the associations between baseline influenza virus–specific hemagglutination inhibition (HAI) and microneutralization (MN) titers and subsequent symptomatic influenza virus infection in a controlled human infection study. Methods We inoculated unvaccinated healthy adults aged 18–49 years with an influenza A/California/04/2009/H1N1pdm-like virus (NCT04044352). We collected serial safety labs, serum for HAI and MN, and nasopharyngeal swabs for reverse-transcription polymerase chain reaction (RT-PCR) testing. Analyses used the putative seroprotective titer of ≥40 for HAI and MN. The primary clinical outcome was mild-to-moderate influenza disease (MMID), defined as ≥1 postchallenge positive qualitative RT-PCR test with a qualifying symptom/clinical finding. Results Of 76 participants given influenza virus challenge, 54 (71.1%) experienced MMID. Clinical illness was generally very mild. MMID attack rates among participants with baseline titers ≥40 by HAI and MN were 64.9% and 67.9%, respectively, while MMID attack rates among participants with baseline titers <40 by HAI and MN were 76.9% and 78.3%, respectively. The estimated odds of developing MMID decreased by 19% (odds ratio, 0.81 [95% confidence interval,.62–1.06]; P =.126) for every 2-fold increase in baseline HAI. There were no significant adverse events. Conclusions We achieved a 71.1% attack rate of MMID. High baseline HAI and MN were associated with protection from illness. Clinical Trials Registration.  NCT04044352. [ABSTRACT FROM AUTHOR]

Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotics. We examined the gastrointestinal microbiota in children treated with β-lactams for community-acquired pneumonia. Data were from 66 children (n = 198 samples), aged 6-71 months, enrolled in the SCOUT-CAP trial (NCT02891915). AAD was defined as ≥1 day of diarrhea. Stool samples were collected on study days 1, 6-10, and 19-25. Samples were analyzed using 16S ribosomal RNA gene sequencing to identify associations between patient characteristics, microbiota characteristics, and AAD (yes/no). Nineteen (29%) children developed AAD. Microbiota compositional profiles differed between AAD groups (permutational multivariate analysis of variance, P < .03) and across visits (P < .001). Children with higher baseline relative abundances of 2 Bacteroides species were less likely to experience AAD. Higher baseline abundance of Lachnospiraceae and amino acid biosynthesis pathways were associated with AAD. Children in the AAD group experienced prolonged dysbiosis (P < .05). Specific gastrointestinal microbiota profiles are associated with AAD in children. [ABSTRACT FROM AUTHOR]

Background. Dose-sparing strategies are being explored for vaccines against pandemic influenza. We evaluated the dose-sparing potential of aluminum hydroxide (AlOH) adjuvant. Methods. A total of 600 healthy subjects (age, 18-49 years) were randomized to receive 2 vaccinations 1 month apart with subvirion inactivated influenza A/H5N1 vaccine containing 7.5, 15, or 45 μg of hemagglutinin (HA), with or without 600 μg of aluminum hydroxide (AlOH), or 3.75 μg of HA, with or without 300 μg of AlOH. Serum specimens were obtained for antibody assays before and 1 month after each vaccination. Results. All formulations were safe. Injection site discomfort was more frequent in groups given vaccines with AlOH. Dose-related increases in antibody responses were noted after both vaccinations (P < .001): geometric mean titers of hemagglutination inhibition antibody in vaccines with and without AlOH, respectively, were 5.4 and 5.4 for subjects who received 3.75 μg of HA, 7.7 and 5.3 for those who received 7.5 μg of HA, 8.1 and 8.5 for those who received 15 μg of HA, and 14.8 and 12 for those who received 45 μg of HA. A ⩾4-fold increase in titer was observed in 2% and 2% of subjects who received 3.75 μg of HA with or without AlOH, respectively; in 14% and 0% who received 7 μg of HA; in 14% and 13% who received 15 μg of HA; and in 33% and 25% who received 45 μg of HA. Addition of AlOH enhanced responses only for subjects who received 7.5 μg of HA, but responses in subjects who received 7.5 μg of HA without AlOH were unexpectedly low. Conclusion. Overall, a meaningful beneficial effect of AlOH adjuvant was not observed. Trial registration. ClinicalTrials.gov identifier: NCT00296634. [ABSTRACT FROM AUTHOR]

An editorial is presented on the improving influenza prevention. Topics inlcude focusing on improving influenza vaccine coverage among older children and younger adults with the lowest coverage percentages reducing influenza illness, increasing accessibility of influenza vaccine through school based vaccination programs might assist with improving coverage in these age groups, and the persons who perceive that influenza vaccine being not effective being less likely to get vaccinated.