meningococcus B & C vaccine

Immunogenicity of Hepatitis B Vaccine in Pediatric Systemic Lupus Erythematosus Patients: ERRATUM.

Madaeng Thanawat T, Soponkanaporn Sirisucha S, Tangnararatchakit Kanchana K, Apiwattanakul Nopporn N et al.

Molecular-level analysis of serum IgG repertoires in COVID-19-vaccinated people with cystic fibrosis identifies abundant convergent antibodies.

Ionov Steven S, Connor Ruth I RI, Curtis Nicholas C NC, Shin Seungmin S et al.

People with cystic fibrosis (pwCF) are at increased risk of severe disease following respiratory viral infections including influenza and respiratory syncytial virus, and were therefore given priority for COVID-19 vaccination. Retrospective epidemiological data have revealed a lower incidence of SARS-CoV-2 infection and a reduced fatality rate among pwCF than in the general population, possibly from the stringent infection control measures and early adoption of protective behaviors. Despite several reports of adequate binding and neutralizing titers after vaccination, the molecular features of vaccine-elicited serum antibody repertoires in pwCF remain unknown. We performed high-resolution proteomic analysis of serum IgG, combined with next-generation sequencing of B cells, to quantitatively profile Spike (S)-reactive serological repertoires from nine infection-naïve pwCF after two doses of COVID-19 mRNA vaccine. We recombinantly expressed 20 IgG clonotypes from 6 pwCF as monoclonal antibodies (mAbs) and measured their binding and neutralization against vaccine-strain and variant viruses. All donors mounted strong binding and neutralizing titers to vaccine-strain virus. Ig-Seq revealed diverse serum repertoires in all vaccinees, with antibodies targeting the receptor-binding domain (RBD) comprising 64% of each circulating repertoire by abundance. Several serum IgG clonotypes identified across our cohort shared identical or similar IGHV and CDRH3 amino acid sequences with serum IgG from other pwCF or S-reactive mAbs isolated from non-CF individuals. These 'convergent' antibodies made up 14.6% of the anti-S repertoires in our cohort, reaching 24.8% in one pwCF. Convergent antibodies tended to be RBD-reactive and enriched in specific IGHV ; surprisingly, a higher abundance of convergent antibodies in serum correlated with a lower breadth of serum neutralization. All 20 mAbs bound Wuhan S with high affinity (EC 50 < 10 nM), and only RBD-reactive mAbs conferred neutralization to vaccine or variant pseudovirus. While most mAbs bound both the B.1.617.2 (Delta, 17/20) and B.1.1.529 (Omicron, 12/20) strains, convergent mAbs were less likely to bind either variant. Post-vaccine serum IgG repertoires in pwCF are dominated by RBD-focused, high-affinity antibodies and include a substantial convergent component shared with non-CF vaccinees. These findings demonstrate that pwCF mount antibody responses comparable to the general population, and a large group of convergent antibodies may contribute to strain-specific rather than cross-variant immunity.

Design and immunoinformatics characterization of a novel multi-epitope vaccine rPRRSV-35N targeting NADC30-like and NADC34-like porcine reproductive and respiratory syndrome virus variants.

Xu Dawei D, Wang Hefei H, Li Miao M, Zhang Ying Y et al.

Porcine reproductive and respiratory syndrome (PRRS), caused by the genetically diverse porcine reproductive and respiratory syndrome virus (PRRSV), remains a major economic burden to the global swine industry. Current commercial vaccines, including modified live virus (MLV) and inactivated vaccines, have shown limited effectiveness against newly emerging PRRSV variants, particularly NADC30-like and NADC34-like strains. There is therefore a need for improved vaccine strategies targeting these circulating strains. In this study, we used immunoinformatics approaches to design a multi-epitope vaccine candidate, rPRRSV-35N, against PRRSV NADC30-like and NADC34-like strains, based on antigenic profiling and prediction of T- and B-cell epitopes. This multi-epitope vaccine candidate integrates six cytotoxic T lymphocyte (CTL) epitopes, three helper T lymphocyte (HTL) epitopes, and seven linear B-cell epitopes (LBE). The epitopes were linked sequentially by flexible linkers. Porcine β-defensin-2 (PBD-2) and PADRE epitopes were incorporated to potentially improve immunogenicity. In silico prediction showed an antigenicity score of 0.6597 and a solubility probability of 0.530. It showed no toxicity or allergenicity, with a molecular weight of 36.64 kDa and a theoretical isoelectric point (pI) of 9.81. Molecular docking and normal mode analysis indicated stable interactions with TLR2 and TLR4 receptors. Immunoinformatics simulations further revealed that the candidate has the potential to induce both humoral and cellular immune responses. The construct was designed for in silico cloning into pET28a(+), and the plasmid was commercially synthesized. Following transformation of the synthetic plasmid into E. coli BL21(DE3), protein expression was verified by Western blot analysis. This study constructed the multi-epitope vaccine candidate rPRRSV-35N targeting NADC30-like and NADC34-like PRRSV strains. Its expressibility was preliminarily verified via molecular cloning and protein expression assays. Further in vivo studies are required to assess its protective efficacy.

Post-vaccination expansion of extrafollicular Th10 and regulatory Tfr cells distinguishes strong from weak influenza vaccine responses in older adults.

Mahajan Avinash S AS, Ravichandran Sathyabaarathi S, Marches Radu R, Yazici Yilmaz Yucehan YY et al.

Despite the superior efficacy of high-dose influenza vaccines, over one-third of older adults fail to respond. Yet, the mechanisms underlying this impaired vaccine responsiveness remain poorly understood. Here, we performed longitudinal profiling of older adults (n=60) receiving high-dose influenza vaccination to identify immune programs associated with vaccine responsiveness. Strong responders exhibited a primed baseline immune state characterized by elevated plasma cytokines and chemokines, followed by enhanced IFN-γ responses and coordinated transcriptional and epigenetic activation of cDC2 cells at day 1. By day 7, CD4⁺ T-cell trajectories diverged: strong responders preferentially expanded influenza-specific activated cTfh1 ( CXCR5 + CXCR3 + ICOS + CD38 + ) and influenza-specific Th10 ( CXCR5⁻ CXCR3 + PD1 + IL10⁺ ) cells, whereas weak responders expanded regulatory cTfr ( CXCR5⁺ FOXP3⁺ ) cells. Th10 expansion correlated with plasmablast and antibody responses and was independently validated in a larger influenza vaccination cohort, including younger adults. Functionally, Th10 cells promoted memory B-cell differentiation into plasmablasts and production of influenza-specific IgGs. TCR analyses revealed minimal clonal overlap between Th10 and cTfh1 cells. Together, these findings identify divergent helper and regulatory CD4⁺ T cell programs associated with vaccine responsiveness and establish Th10 cells as a previously unrecognized component of vaccine-induced humoral immunity.