Nontypeable (NTHi) is a major cause of community acquired pneumonia and exacerbation of chronic obstructive pulmonary disease. A current effort in NTHi vaccine development has focused on generating humoral responses and has been greatly impeded by antigenic variation among the numerous circulating NTHi strains. In this study, we showed that pulmonary immunization of mice with killed NTHi generated broad protection against lung infection by different strains. While passive transfer of immune antibodies protected only against the homologous strain, transfer of immune T cells conferred protection against both homologous and heterologous strains. Further characterization revealed a strong Th17 response that was cross-reactive with different NTHi strains. Responding Th17 cells recognized both cytosolic and membrane-associated antigens, while immune antibodies preferentially responded to surface antigens and were highly strain specific. We further identified several conserved proteins recognized by lung Th17 cells during NTHi infection. Two proteins yielding the strongest responses were tested as vaccine candidates by immunization of mice with purified proteins plus an adjuvant. Immunization induced antigen-specific Th17 cells that recognized different strains and, upon adoptive transfer, conferred protection. Furthermore, immunized mice were protected against challenge with not only NTHi strains but also a fully virulent, encapsulated strain. Together, these results show that the immune mechanism of cross-protection against pneumonia involves Th17 cells, which respond to a broad spectrum of antigens, including those that are highly conserved among NTHi strains. These mechanistic insights suggest that inclusion of Th17 antigens in subunit vaccines offers the advantage of inducing broad protection and complements the current antibody-based approaches.

dsRNA can be detected by pattern recognition receptors, for example, TLR3, MDA-5, NLRP3 to induce proinflammatory cytokines responsible for innate/adaptive immunity. Recognized by endosomal TLR3 in myeloid DCs (mDCs), dsRNA can activate mDCs into mature antigen presenting cells (mAPCs) which in turn present antigen epitopes with MHC-I molecules to naïve T cells. Coadministration of protein and synthetic dsRNA analogues can elicit an antigen-specific Th1-polarized immune response which stimulates the CD8+ CTL response and possibly dampen Th17 response. Synthetic dsRNA analogues have been tested as vaccine adjuvant against viral infections in animal models. However, a dsRNA receptor, TLR3 can be expressed in tumor cells while other members of TLR family, for example, TLR4 and TLR2 have been shown to promote tumor progression, metastasis, and chemoresistance. Thus, the promising potential of dsRNA analogues as a tumor therapeutic vaccine adjuvant should be evaluated cautiously.

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Background Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is widely used as a curative treatment strategy for most types of hematological diseases. However, strategies for enhancing the graft versus leukemia (GVL) effect without aggravating the graft versus host disease (GVHD) effect are still being pursued. Methods A retrospective cohort study was performed to compare the outcomes between combined unrelated umbilical cord blood (UCB-haplo HSCT) and haplo HSCT. Results The results showed that neither acute GVHD (aGVHD) nor chronic GVHD (cGVHD) was increased in the UCB-haplo HSCT group, and the engraftment and infection rates were similar between the two groups. However, overall survival and progression-free survival were significantly improved, while transplantation-related mortality and relapse were significantly decreased in the UCB-haplo HSCT group by both univariate and multivariate analyses. Conclusion Our results indicated that the addition of a UCB unit could improve the prognosis of haplo-HSCT and enhance the GVL effect without increasing the incidence of GVHD. Trial registration The cohort study was retrospectively registered at https://www.chictr.org.cn as ChiCTR2100046681.

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