Multiple monovalent COVID-19 PHH-1V vaccine adaptations elicit homologous and cross-neutralizing antibody responses in mice.

SARS-CoV-2 Ancestral and Omicron variant immunity in Australian children in 2023, a seroprevalence study.

Intranasal administration of a DNA vaccine complexed with sugar-functionalized chitosan induces protective immunity against SARS-CoV-2 in mice.

Current coronavirus disease 2019 (COVID-19) vaccines effectively prevent severe disease but induce primarily systemic immunity without mucosal protection in the respiratory tract, which is mandatory for protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the prevention of viral transmission. Vaccination strategies capable of inducing local immunity at the site of infection are therefore needed. Here, we evaluated a poly (lactic-co-glycolic acid) (PLGA) microparticle-based vaccine co-encapsulating the receptor binding domain (RBD) of SARS-CoV-2 Spike protein with the TLR3/RIG-1 agonist Riboxxim, employing a subcutaneous prime and intranasal boost immunization schedule. BALB/c mice received subcutaneous prime immunization followed by intranasal boost with PLGA microparticles containing RBD/Riboxxim. Antibody responses were assessed by enzyme-linked immunosorbent assay (ELISA), neutralization by competitive ELISA and T-cell responses by enzyme-linked immune spot assay, intracellular cytokine staining and flow cytometry. Memory responses were evaluated 30 days post boost immunization. Vaccination induced robust RBD-specific IgG and IgA antibody titres in both serum and bronchoalveolar lavage fluid, with neutralizing capacity against the Wuhan-Hu-1 strain. Strong CD4+ and CD8+ T-cell responses were detected systemically and in the respiratory tract. Importantly, the vaccine generated durable immunological memory, including tissue-resident memory T-cells in the respiratory tract and long-lived IgG and IgA memory B-cells in secondary lymphoid organs. PLGA microparticle-based vaccination induces potent systemic and mucosal immune responses against SARS-CoV-2 RBD. This adaptable platform represents a promising approach for mucosal vaccination strategies, with potential for rapid adaptation to emerging variants.

Few data are available comparing the WHO diphtheria-tetanus-pertussis (DTP)-containing vaccine schedule with reduced-dose or delayed three-dose schedules in infants. We aimed to identify an alternative schedule that is non-inferior or superior to the WHO schedule in maintaining early pertussis antibody levels before booster, while creating space for integration of new vaccines. In two parallel, open-label, randomised, non-inferiority trials in Uganda and Nepal, healthy infants aged 42-50 days were randomised in a 4:4:4:3:3 ratio via an online system to five diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae type b-hepatitis B (DTwP-Hib-HepB) vaccination schedules (WHO schedule [ages 6, 10, and 14 weeks]; reduced two-dose schedules at ages 6 and 14 weeks or ages 2 and 4 months; or delayed three-dose schedules at ages 2, 3, and 4 months or ages 2, 4, and 6 months), using site-stratified block randomisation with a block size of 18. The primary outcome was the pre-booster IgG antibody response against pertussis antigens (pertussis toxin; filamentous haemagglutinin [FHA]; pertactin; fimbriae 2 and 3 [Fim 2 and 3]). Antibody responses during and 1 month after the primary series were assessed as secondary endpoints. The two-dose schedules were compared with the WHO schedule as primary analyses, and the exploratory analyses were to compare delayed three-dose schedules with the WHO schedule. All these analyses were conducted in the per-protocol population. For the primary endpoint, non-inferiority margins for geometric mean ratios (GMRs) between two-dose and WHO schedules were calculated for each pertussis antigen separately as 35% of the standard deviation of the geometric mean concentrations of the WHO group, and non-inferiority was concluded if the lower bound of the 95% CI of the GMR exceeded the non-inferiority margin. A non-inferiority margin of 0·67 was used for all other non-inferiority comparisons. The trials were registered with ISRCTN (Uganda [ISRCTN60356654] and Nepal [ISRCTN12240140]) and are complete. Between Oct 1, 2021, and July 12, 2022 (Uganda) and Dec 5, 2021, and Feb 26, 2023 (Nepal), 956 infants were recruited per country and randomly allocated across the five study groups; pre-booster analyses were conducted in 876 participants in Uganda and 851 participants in Nepal. Two-dose schedules at ages 6 and 14 weeks and ages 2 and 4 months did not meet non-inferiority criteria for pertussis antibodies pre-booster, except FHA (non-inferiority margin 0·59) in Nepal (6 and 14 weeks GMR 0·83 [95% CI 0·61-1·13]; 2 and 4 months 1·20 [0·88-1·64]). Delayed three-dose schedules at ages 2, 3, and 4 months and ages 2, 4, and 6 months produced similar or higher post-primary series and pre-booster responses compared with the WHO schedule, but the WHO schedule achieved higher antibody responses against all pertussis antigens, except FHA in Nepal, at age 3 months. The WHO DTP schedule is the preferred schedule in high-pertussis-burden settings, as it elicits the greatest antibody responses in the first 3 months of life when infants are particularly vulnerable. Although delayed three-dose schedules may be considered in low-risk contexts and in settings with maternal immunisation programmes, early infant protection should guide policy decisions. Gates Foundation.

Real-world effectiveness and antibody responses of BNT162b2 vaccination in long-term care residents: A retrospective case-control study.

In case of emerging or re-emerging infections, vaccine platform technologies are needed to rapidly develop effective vaccines to aid public healthcare in pandemics. Besides mRNA vaccines, also viral platform technologies, that is, the adenovirus-derived vaccines Vaxzevria and JCOVDEN, have proven to be of immense value during the COVID-19 pandemic. For future pandemics, it is crucial to understand the factors in vector design that modulate immunogenicity. This knowledge allows the tailoring of vaccine vectors to fit specific target product profiles, for example, to build vectors which trigger an accentuated T cell or, alternatively, antibody response against an antigen of interest. Our study using the live-attenuated measles vaccine backbone as a promising example is therefore crucial in demonstrating that very minor differences in the vaccine backbone can alter the antigen expression profile of the vector-antigen system and impact the relative induction of T-cell or antibody responses against the added target antigen.

Introduction Allogeneic hematopoietic cell transplantation (alloHCT) recipients are at increased risk of severe COVID-19. Although vaccination is strongly recommended, immune responses may vary and can be affected by clinical and treatment-related factors. Methods In this longitudinal, single-center study, we analyzed IgG, IgM, and IgA antibody kinetics to severe acute respiratory syndrome-Corona virus-2 (SARS-CoV-2) spike-1, receptor binding domain (RBD), and nucleocapsid proteins in 354 alloHCT patients and 647 healthy controls by ELISA. A total of 1,364 serum samples were collected before and after one, two, and three doses of mRNA, adenovirus vector, and/or protein-based vaccines. Clinical parameters, including age, conditioning regimen, immunosuppressive therapy, graft-versus-host disease (GVHD), donor type, time since transplantation, diagnosis, and laboratory parameters were evaluated for their influence on antibody responses. Results Anti-spike-1 IgG responses increased progressively: 27% of patients versus 28% of controls seroconverted after the first vaccination, 65% versus 59% after the second, and 93% versus 98% after the third. After three doses, no significant differences in IgG prevalence or reactivity remained between groups. IgM and IgA responses were infrequent. Multivariate analysis identified diagnosis, shorter interval between transplantation or vaccination and antibody testing, and lower lymphocyte count as negative predictors after the first vaccination. No negative predictors were detected after the third dose. Antibody levels remained stable for at least six months following the third vaccination. Breakthrough infections occurred but were mild. Conclusions AlloHCT recipients achieve humoral immunity comparable to healthy individuals after three vaccine doses, supporting efficacy and safety of repeated SARS-CoV-2 vaccination in this vulnerable population.

Serum antibody levels against microbial biomarkers of periodontitis, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, are associated especially with the presence of these species in the oral cavity. We investigated the genetic basis of host antibody responses against these species through a genome-wide association study (GWAS) to identify the genetic determinants of this immune reactivity. Serum immunoglobulin A (IgA) and immunoglobulin G (IgG) antibody levels against A. actinomycetemcomitans and P. gingivalis were determined using multiserotype enzyme-linked immunosorbent assay in 3,719 participants from 4 Finnish cohort studies: FinnTwin, Parogene, FINRISK97, and Health-2000. The associations of genetic polymorphisms and imputed human leukocyte antigen (HLA) alleles with antibody levels were investigated. All antibody levels presented significant increasing trends with periodontitis stage and grade. A. actinomycetemcomitans IgG displayed association with single nucleotide polymorphisms (SNPs) in chromosome 6 with lead SNP rs574581129 (near HLA-DRB1, P = 3.6 × 10-8) and P. gingivalis IgG in chromosome 14 with lead SNP rs146761521 (near NUBPL, 5.5 × 10-8). In addition, all antibody levels presented suggestive associations with several loci. Detailed HLA analyses revealed that A. actinomycetemcomitans IgG was associated with DQA1*01:01, DQB1*05:01, and DRB1*01:01 and P. gingivalis IgG with HLA-A*02:01 alleles. Both IgA and IgG antibody levels against microbial biomarker species of periodontitis increase with periodontitis stage and grade, but genetic variation is also a significant predictor. Specific alleles within the HLA region may influence antibody responses to A. actinomycetemcomitans and P. gingivalis, highlighting potential genetic contributions to the immunological mechanisms underlying periodontitis.

Genome-wide association study for the detection of genetic variants associated with the antibody response upon viral hemorrhagic septicemia virus vaccination in Paralichthys olivaceus.

Organic acidemias (OAs) are a group of inherited disorders, most commonly caused by defects in mitochondrial enzymes involved in amino acid and fatty acid metabolism. While they characteristically present with metabolic and neurological crises, growing evidence reveals a significant burden of chronic immune dysregulation in some disorders and patients. This review provides a synthesis of clinical and mechanistic evidence discussing immune dysregulation in OAs. Cytopenia can occur in OAs and predispose patients to recurrent and severe infections. Adaptive immune deficits, such as hypogammaglobulinemia, reduced B and T cell populations, and impaired vaccine-specific antibody responses, including to diphtheria and tetanus in MSUD and to the inactivated COVID-19 vaccine in propionic acidemia, have also been reported. Additionally, some case series note hyperinflammatory conditions, such as hemophagocytic lymphohistiocytosis. Mechanistic studies indicate that accumulated metabolites disrupt innate and adaptive hematopoietic progenitor function, mitochondrial homeostasis, and inflammatory signaling. Emerging therapeutic avenues, such as gene and mRNA-based therapies, hold the potential to improve or normalize the biochemical phenotype in OAs. While their impact on immune abnormalities remains largely unexplored, future clinical trials offer an opportunity to systematically assess potential effects on immune parameters. OAs are increasingly recognized as disorders with intrinsic immune dysregulation, extending beyond their well-characterized metabolic and neurological manifestations. Future clinical trials will benefit from including immunological endpoints to evaluate immunological recovery for novel therapies.

Expression of pseudorabies virus glycoproteins E and B based on vaccinia virus.

Serological progression and time to seroconversion in serodiscordant and seronegative dogs tested for visceral leishmaniasis in an endemic area of Brazil.

Targeted mutagenesis of the ICP4 transactivation domain generates a protective DIVA vaccine against duck plague.

Generation and characterization of the monoclonal antibody against the heavy chain of American eel (Anguilla rostrata) IgM.

BECC-adjuvanted hemagglutinin influenza vaccine promotes enhanced immunogenicity and protective efficacy.

Dengue is caused by infection with 1 of 4 dengue virus (DENV) serotypes (DENV-1 to DENV-4). V181 and Butantan-Dengue Vaccine (Butantan-DV) are independently developed, single-dose, quadrivalent dengue vaccines based on the same attenuated parental strains. In this randomized, double-blind, active comparator-controlled, multisite, phase 2 trial, we compared the safety and immunogenicity of V181 and Butantan-DV in healthy adults in Brazil. The primary immunogenicity objectives were to compare vaccine-induced neutralizing antibody geometric mean titers (GMTs) and seroconversion rates for DENV-1 to DENV-4 at day 28 postvaccination. The primary and secondary safety objectives, respectively, were to assess vaccine-related serious adverse events and the proportion of participants experiencing solicited adverse events through day 28 postvaccination. Overall, 1364 participants were assigned (1:1) to receive V181 (n = 682) or Butantan-DV (n = 682). At day 28 postvaccination, V181 induced a noninferior immune response to Butantan-DV for DENV-1 and DENV-2 but not DENV-3 and DENV-4, as measured using GMT ratios. Noninferiority was established for all DENV serotypes based on seroconversion rates. Most participants developed a trivalent or tetravalent neutralizing antibody response. Vaccine viremia was detected for each DENV serotype. V181 and Butantan-DV were generally well tolerated. V181 was immunogenic in adults, and while immunogenicity was noninferior to Butantan-DV for DENV-1 and DENV-2, seroconversion rates were noninferior for DENV-1 to DENV-4. The safety profile of V181 is comparable to that of Butantan-DV and supports its continued evaluation as a single-dose quadrivalent vaccine for dengue prevention. NCT05710224.

Development of a recombinant chimeric Newcastle disease virus-vectored vaccine conferring single-dose, triple protection against genotype VII NDV, IBDV, and H9N2 AIV.

Development of an ELISA-based pulldown approach for functional analysis of antigen-specific antibodies.

Development and evaluation of a P. multocida A-M. haemolytica A6-rLkt combined vaccine for enhanced control of bovine respiratory disease complex.