Vaccines最新文献

The scientific literature is quite rich when it comes to vaccines and vaccination: just by looking at PubMed, using as "Vaccin* [Title/Abstract]" a search key, it is possible to obtain more than 480,000 results starting from 1799, and more than 25,288 results were published in the last year [...].

Background: West Nile Virus (WNV) is a mosquito-borne flavivirus responsible for seasonal outbreaks in temperate and tropical regions, including Europe, the Mediterranean, and the Middle East. Its transmission via mosquitoes, particularly Culex species, poses persistent challenges to public health. Despite ongoing efforts, comprehensive prevention and treatment strategies remain limited. Methods: A comprehensive search of peer-reviewed literature, clinical trials, and government surveillance data from Italy and Iran was conducted using PubMed, Scopus, Web of Science, and supplementary web-based resources. Inclusion criteria focused on molecular studies of WNV, vaccine and antiviral drug development, and regional outbreak reports. Results: WNV transmission is influenced by climatic conditions, as well as vector distribution and ecological patterns. While human vaccines are currently under development, only veterinary vaccines yielded promising but still limited evidence of effectiveness. Notably, therapeutic measures are currently limited to supportive care, whereas investigational antiviral drugs are in early-stage trials. Interestingly, Italy demonstrates robust surveillance with regular reporting of outbreaks, whereas data from Iran indicate that despite a widespread serological footprint, especially in southern and southwestern provinces, the reported clinical impact on humans and animals appears comparatively less severe. Conclusions: Bridging gaps in vaccine availability, therapeutic innovation, and disease monitoring is essential for effective WNV management to prepare for potential severe future outbreaks in Europe and the Middle East. On the other hand, regional differences between Italy and Iran reveal the need not only for tailored public health interventions and enhanced surveillance, but also for sustained investment in research. In our view, collaborative frameworks across Mediterranean and Middle Eastern countries in a "One Health" approach may improve preparedness and response to future WNV outbreaks.

Background: A major goal for the vaccine field is the elicitation of broadly neutralizing antibodies (bnAbs) against pathogens that exhibit extensive antigenic diversity.

Methods: In this study, we designed a rigid divalent immunogen for high avidity binding to the bnAb, VRC01, which targets the CD4 binding site (CD4bs) of the HIV spike protein. This was accomplished by covalently linking two HIV-1 gp120 antigens to a complementary antibody and crosslinking the light chains. Binding kinetics were analyzed using a novel gel shift assay and surface plasmon resonance.

Results: The rigid divalent immunogen exhibits a higher affinity for VRC01-class antibodies compared to a flexible control, likely due to antigen pre-organization limiting the entropic penalty for divalent binding. Crucially, this immunogen exhibited divalent binding to VRC01 and monovalent binding to a non-CD4bs Ab, A32-a characteristic we refer to as "selective avidity."

Conclusions: In light of these results, we are preparing for in vivo vaccination experiments to test the immune focusing properties of this immunogen, the results of which may suggest broad application of the selective avidity concept.

Background: Seasonal influenza remains a significant public health problem, and the constant antigenic drift of viruses requires regular vaccine updates. mRNA vaccines offer a promising platform for the development of new, effective influenza vaccines. Administration of the naked mRNA vaccine using a needle-free jet injection system further enhances its safety, reduces cost, and eliminates the need for lipid nanoparticles, which are traditionally used for mRNA delivery. Lyophilization of naked mRNA allows for long-term storage at +4 °C. Methods: We designed and produced an mRNA vaccine against seasonal influenza, designated mRNA-Vector-Flu, encoding the hemagglutinin (HA) of the A/Wisconsin/67/2022(H1N1)pdm09, A/Darwin/9/2021(H3N2), and B/Austria/1359417/2021 strains. The vaccine was lyophilized and stored for 1 month in a refrigerator (+4 °C). A comparative immunogenicity study was conducted between synthesized immediately before use prepared and lyophilized naked mRNA-Vector-Flu. The preparations were administered to BALB/c mice using a jet needleless injection twice, 3 weeks apart. Immunogenicity was assessed on day 35 of the study. Results: A comparative immunogenicity study of naked mRNA-Vector-Flu demonstrated that both the synthesized immediately before use prepared formulation and the lyophilized form, stored at +4 °C for a month, induced similar levels of virus-specific antibodies and generated a pronounced T-cell immune response. Conclusions: Delivery of the naked mRNA vaccine using a needle-free jet injection ensures a high-level immune response, which improves its safety, reduces its cost, and eliminates the need for lipid nanoparticles traditionally used for mRNA delivery. At the same time, lyophilization of the naked mRNA vaccine preserves its biological activity and ensures its storage for at least a month at +4 °C temperatures. Our results demonstrate that our proposed approach can be considered a promising direction for the development and improvement of the mRNA vaccine platform.

Background: The development of effective tuberculosis (TB) vaccines beyond BCG remains an urgent global health priority, especially for prevention of pulmonary TB in adults. While most current strategies focus on enhancing T-cell immunity, the potential of trained immunity to broadly augment both innate and adaptive responses remains underexplored in TB vaccinology. Given the central role of dendritic cells (DCs) as bridges between innate and adaptive immunity, we hypothesized that inducing trained immunity in DCs could optimize subsequent T-cell responses. Previous studies have identified Rv2299c as a promising adjuvant of other antigens by promoting DC maturation; however, whether it could be used as a standalone protective antigen of TB vaccine remains unclear. Methods: We constructed a chimpanzee adenovirus-vectored TB vaccine candidate expressing Rv2299c (rAd-Rv2299c), and evaluated its immunogenicity and protective efficacy in murine models. Results: rAd-Rv2299c vaccine effectively induced a trained immunity phenotype in DCs, as evidenced by upregulated MHC-II and CD86 expression and increased pro-inflammatory cytokine (TNF-α, IL-6, IL-1β and IL-12p70) secretion. Moreover, its immunization promoted the generation of antigen-specific polyfunctional T cells, and robustly enhanced both Th1 and Th17-type immune responses. In a murine challenge model, vaccination significantly reduced bacterial loads in the lung and spleen and attenuated pulmonary inflammation, which was associated with robust recall T-cell immune responses. Conclusions: rAd-Rv2299c confers anti-TB protection by inducing trained immunity in DCs and promoting polyfunctional T-cell responses, thereby offering valuable experimental evidence and conceptual insights for the development of next-generation TB vaccines.

Leishmaniasis is an infectious disease caused by several species of Leishmania parasites that preferentially infect macrophages as host cells. These intracellular parasites can evade the main microbicidal effector mechanisms of phagocytic cells and, in turn, are able to stimulate marked Th2 or regulatory T cell immune responses, which are not protective for the host. The presence of a non-protective immune response, together with the multiplication and spread of Leishmania parasites throughout the tissues, leads to the main clinical forms of leishmaniasis, such as cutaneous and visceral leishmaniasis. Although some clinical forms can be reproduced in experimental hosts such as mice and hamsters, these models do not fully mimic natural infection, which, in fact, impacts experimental vaccine development. For example, BALB/c mice are generally infected with around one million parasites, whereas humans are not infected with more than 1000 parasites, together with vector saliva. This excessive number of parasites in experimental models may affect the efficacy of vaccines in preclinical studies. Indeed, many experimental studies conducted over the past 20 years have shown only partial protection, regardless of the vaccine generation, host species employed, or the use of adjuvants. This review aims to summarize the main aspects associated with Leishmania vaccine development, including parasite diversity, host factors, immune responses, adjuvants, and antigens. Although many elegant studies have been conducted, it is possible that some essential step is still missing for the development of an effective vaccine for human use.

Extraintestinal pathogenic Escherichia coli (ExPEC) is a major cause of infections of the urinary tract, the bloodstream, and other non-intestinal sites in humans. ExPEC often resists the bactericidal action of human immune defenses including complement, antimicrobial peptides, antibodies, and cell-mediated killing. This review provides an overview of the main host defense strategies, and the mechanisms and molecules ExPEC engages to resist these human immune responses. Surface-exposed polysaccharides, outer membrane proteins, cytotoxins, and proteases are all part of the bacterial arsenal of defenses that can neutralize many of the host's immune defenses. These factors work in concert to enable ExPEC to survive and thrive in extraintestinal environments of the human body.

Background/Objectives: Viral hepatitis remains a significant global cause of chronic liver disease, highlighting the importance of effective vaccination strategies. This review assesses recent evidence on vaccine safety and effectiveness. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Scopus identified English-language studies published from January 2000 to September 2025. Eligible studies evaluated vaccination for hepatitis A, B, C, or E, as well as vaccine responses in individuals with chronic liver disease or HIV infection. Of 5254 records screened, 166 studies met the inclusion criteria. Results: Hepatitis A vaccines demonstrated excellent safety, 95-100% short-term seroprotection, and durable immunity for both inactivated and live-attenuated formulations, with population-level reductions in disease incidence. Hepatitis B vaccines showed consistently strong immunogenicity across age groups, with over 90% seroprotection from recombinant and CpG-adjuvanted formulations. Effective prevention of mother-to-child transmission required maternal antiviral therapy, timely birth-dose vaccination, hepatitis B immunoglobulin (HBIG) administration, and post-vaccination serologic testing. Long-term data demonstrated immune persistence for up to 35 years and significant reductions in liver cancer following neonatal HBV vaccination. Limited studies in hepatitis C populations showed impaired responses, partially improved with higher or booster doses. Hepatitis E vaccines showed excellent safety and over 99% seroconversion. In non-viral liver disease and post-transplant populations, vaccine responses were reduced but remained clinically meaningful, especially with adjuvanted or higher-dose HBV vaccines. Among HIV-infected individuals, HAV vaccination was generally effective, while enhanced HBV regimens markedly improved seroprotection. Conclusions: Hepatitis A, B, and E vaccines are safe, immunogenic, and effective, with neonatal hepatitis B vaccination critical for preventing maternal transmission. No licensed HCV vaccine exists, and therapeutic HCV vaccines show limited efficacy. Optimized and targeted vaccination strategies are needed for individuals with chronic liver disease, HIV infection, HCV infection, transplant recipients, and other immunocompromised populations to maximize public health impact.

Background: Women's empowerment has been significantly associated with improved child health outcomes. Cambodia, amid a rapid socioeconomic transition, offers a critical setting to examine how advancements in women's empowerment over the past decade have influenced child immunization completion within the first two years of life. Methods: Data from the Cambodia Demographic and Health Surveys conducted in 2010, 2014, and 2021-22, encompassing 9222 women with recent births, were analyzed. Empowerment was measured across literacy and information access, employment, and decision-making domains. Multinomial logistic regression assessed associations between empowerment factors and completion of oral polio (OPV), diphtheria-tetanus-pertussis (DTP), pneumococcal conjugate (PCV), and measles-rubella (MR) vaccines, adjusting for demographic and socioeconomic variables. Results: Between 2010 and 2022, women's empowerment in Cambodia improved significantly, marked by higher literacy rates, nearly half of women completing primary education, and expanded digital access, with 82.4% owning mobile phones and approximately 50% using the internet daily. While non-working women slightly increased, agricultural employment declined by 20%, and cash earnings rose from 48.7% to 82.5%. Most women participated in major household decision-making, either independently or jointly. Completion rates for OPV, DTP, and PCV ranged from 79% to 83%, while just over half of children were fully vaccinated against measles. Higher maternal education and cash earnings were positively associated with OPV, DTP, and PCV completion but negatively associated with measles vaccination. Women in agricultural work were less likely to complete measles vaccination for their children than non-working women. Joint decision-making regarding the use of respondents' income was associated with a higher likelihood of measles non-completion (OR = 2.26, 95% CI: 1.13-4.51), whereas joint decision-making about respondents' health care was associated with a higher likelihood of measles completion (OR = 0.42, 95% CI: 0.21-0.83). Conclusions: Women's empowerment remains a key determinant of vaccination outcomes in Cambodia. The distinct pattern observed for measles suggests that vaccines scheduled for older ages encounter greater structural and behavioral barriers. To overcome these challenges, strategies should focus on enhancing defaulter tracking, implementing reminder systems, expanding outreach and catch-up programs, and improving the convenience of vaccination services.

Background: Norovirus GII.4 is a major global health threat, yet no licensed vaccines exist due to the virus's rapid evolution and high mutation rates. Objective: To rationally design and experimentally validate multi-epitope vaccine candidates against Norovirus GII.4 using computational immunoinformatics and in vivo evaluation. Methods: We employed reverse vaccinology to screen optimal norovirus GII.4 epitopes and systematically designed four construction strategies to evaluate different epitope topologies and adjuvants. Candidates underwent molecular dynamics simulations and were expressed in E. coli. Immunogenicity was assessed in BALB/c mice via ELISA and ELISPOT to evaluate humoral and cellular responses. Results: Three candidates (NV1, NV4, NV5) were successfully produced and induced cross-reactive antibodies against authentic GII.4 virus-like particles. Notably, the construction strategy influenced the immune response: NV5 (repetitive epitopes and HSP as adjuvant) elicited the highest antigen-specific antibody titers, NV1 (all types of epitopes and TLR as adjuvant) induced the strongest cellular response, and NV4 (repetitive epitopes and TLR as adjuvant) achieved the most rapid immune response. Consistently, in silico analysis showed that the NV1-TLR3 complex exhibits tighter interaction, higher binding energy, and greater structural stability, supporting its superior capacity to trigger cellular immunity. Conclusions: A rational multi-epitope vaccine design workflow successfully realized the translation from computational design to functional vaccines. Optimizing adjuvant selection and epitope construction is critical for eliciting immune responses in next-generation norovirus vaccines.