NPJ Vaccines最新文献

Multiple myeloma (MM), a hematological malignancy of the bone marrow, remains largely incurable. The orphan G protein-coupled receptor, GPRC5D, which is uniquely expressed in plasma cells and highly expressed in MM, is a compelling candidate for immunotherapy. In this study, we investigated the efficacy of a combination of DNA vaccine encoding mouse GPRC5D and PD-1 blockade in preventing and treating MM using the 5TGM1 murine model of MM. The mouse vaccine alone was effective in preventing myeloma growth but required PD-1 antibodies to inhibit established MM tumors. We next evaluated the prophylactic and therapeutic efficacy of a nanoplasmid vector encoding human GPRC5D in several murine syngeneic tumor models. Similar results for tumor inhibition were observed, as human GPRC5D-specific T cells and antibodies were induced by DNA vaccines. Taken together, these findings underscore the potential of GPRC5D-targeted DNA vaccines as versatile platforms for the treatment and prevention of MM.

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease associated with its principal tick vector, Hyalomma spp. with increasing fatal incidence worldwide. Accordingly, CCHF is a World Health Organization-prioritized disease with the absence of effective preventive interventions and approved vaccines or effective treatments. This perspective raised from a multidisciplinary gap analysis considering a One Health approach beneficial for human and animal health and the environment exploring international collaborations, gaps and recommendations.

The failure of human vaccine efficacy trials assessing a mosaic HIV-1 vaccine calls into question the translatability of preclinical SHIV challenge studies that demonstrated high efficacy of this vaccine in primates. Here we present a post hoc immune correlates analysis of HIV-1 Env peptide-binding antibody responses from the NHP13-19 study identifying the V2 loop as the principal correlate of protection in primates. Moreover, we found high V2 loop sequence identity between the Mos1 vaccine component and the SHIV challenge strain, while the vaccine showed considerably lower V2 identity to globally circulating HIV-1 sequences. Thus, the induction of immune responses against the V2 epitope, which had exceptional identity between the vaccine and challenge Env strains, may have contributed to the high protection in primates.

T helper cells, particularly T follicular helper (T_FH) cells, are essential for the neutralizing antibody production elicited by pathogens or vaccines. However, in immunocompromised individuals, the inefficient support from T_FH cells could lead to limited protection after vaccine inoculation. Here we showed that the conjugation of inducible T cell costimulatory (ICOS) onto the nanoparticle, together with immunogen, significantly enhanced the immune response of the vaccines specific for SARS-CoV-2 or human immunodeficiency virus type-1 (HIV-1) in T_FH-deficient mice. Further studies indicated that ICOSL on B cells was triggered by ICOS binding, subsequently activated the PKCβ signaling pathway, and enhanced the survival and proliferation of B cells. Our findings revealed that the stimulation of ICOS-ICOSL interaction by adding ICOS on the nanoparticle vaccine significantly substitutes the function of T_FH cells to support B cell response, which is significant for the immunocompromised people, such as the elderly or HIV-1-infected individuals.

Controversies persist about the protective effects of vaccines against acute cardiovascular events. Using electronic medical records from hospitals and influenza vaccine administration data in Beijing, China, we studied individuals vaccinated between January 1, 2016, and December 31, 2018, who experienced at least one acute cardiovascular event within two years. A self-controlled case series design calculated the relative incidence (RI) and 95% confidence interval (CI) of acute cardiovascular events within one year after vaccination. Among 1647 participants (median age: 65 years, 38.43% female), the risk of events 29-365 days post-vaccination was 0.76 times the baseline level (RI: 0.76; 95% CI: 0.68-0.84). The protective effect was more pronounced in younger participants (P = 0.043) and those without cardiovascular history (P < 0.001), while acute respiratory infection (P = 0.986) and vaccination frequency (P = 0.272) had no impact. Influenza vaccines offer protection against acute cardiovascular events for at least one year, suggesting potential for cardiovascular disease prevention.

Mycoplasma gallisepticum (MG) is an avian respiratory pathogen causing significant global economic losses to the poultry industries. Current live-attenuated and bacterin vaccines provide some measures of protective immunity but exhibit suboptimal efficacy, utility, or safety. To address these shortcomings, we utilized knowledge of MG biology and virulence to develop a subunit vaccine containing recombinantly produced primary adhesin GapA, cytadhesin-related molecule CrmA, and four early-phase-expressed variable lipoprotein hemagglutinins (VlhAs) (3.03, 3.06, 4.07, 5.05) of the virulent strain Rlow. The vaccine was tested in chickens using a subcutaneous dose of 50 µg per protein, a prime-boost schedule, and strain Rlow challenge in multiple studies to compare adjuvant formulations. While different adjuvants resulted in variable levels of protection, only CpG oligodeoxynucleotide (CpG ODN 2007) resulted in significant reductions of both MG recovery and tracheal pathology. These results demonstrate that a rationally designed and safe subunit vaccine is efficacious against MG disease.

Vaccines are the most effective and sustainable intervention to control ticks and tick-borne diseases (TBD). Using a personalized vaccine design based on regional tick genotypes, a Rhipicephalus appendiculatus Subolesin protective antigen was used in a field trial evaluating tick vaccine efficacy, effectiveness, and safety in cattle infested with multiple tick species in different Ugandan agro-ecological zones. Vaccination with SUB was safe with a protective capacity against anemia and infection, and reduced the number of infested cattle, tick fitness (feeding and reproduction) with vaccine effectiveness against multiple tick species between 93.2% at 167-196 days post-vaccination (dpv) and 61.4% at 251–327 dpv. Total integrated vaccine efficacy/effectiveness was estimated as 98.8%. The Subolesin-based vaccine is protective against multiple cattle tick infestations under field conditions in Uganda. These results support registration and commercialization of the vaccine to reduce tick populations and associated risks for human and animal TBD and chemical acaracides in Uganda.

Vaccine-induced T cells and neutralizing antibodies are essential for protection against SARS-CoV-2. Previously, we demonstrated that an antigen delivery system, pullulan nanogel (PNG), delivers vaccine antigen to lymph node medullary macrophages and thereby enhances the induction of specific CD8⁺ T cells. In this study, we revealed that medullary macrophage-selective delivery by PNG depends on its binding to a C-type lectin SIGN-R1. In a K18-hACE2 mouse model of SARS-CoV-2 infection, vaccination with a PNG-encapsulated receptor-binding domain of spike protein decreased the viral load and prolonged the survival in the CD8⁺ T cell- and B cell-dependent manners. T cell receptor repertoire analysis revealed that although the vaccine induced T cells at various frequencies, low-frequency specific T cells mainly promoted virus clearance. Thus, the induction of specific CD8⁺ T cells that respond quickly to viral infection, even at low frequencies, is important for vaccine efficacy and can be achieved by SIGN-R1⁺ medullary macrophage-targeted antigen delivery.