Efficient Vaccine Research Articles

The construction of a peptide vaccine with multifunctional DNA tetrahedron exoskeleton

Peptide vaccines have emerged as promising candidates due to their specificity and safety. However, their development faces several challenges, including poor stability, weak immunogenicity, and low delivery efficiency. To address these issues, this study introduces a novel delivery platform that leverages tetrahedral DNA nanostructure (TDN), known for its efficient cell uptake, low immunogenicity, excellent editability, and biocompatibility. Serving as the multi-functional exoskeleton, the TDN integrating peptide antigens and CpG ODNs enhanced antigen stability, dendritic cell uptake, optimized node accumulation, and immunogenicity. Our findings, supported by both in vitro and in vivo evaluations, demonstrated that TDN-based peptide vaccine (denoted as peptide@TPVax) could induce a comprehensive adaptive immune response, including Th-1 biased cellular responses, antibody production and memory response formation, to overcome the existing delivery challenges. Our study laid a theoretical foundation for future vaccine design by presenting a versatile carrier for the development of efficient peptide vaccines. Our in vitro and in vivo evaluations revealed that the TDN-based peptide vaccine (peptide@TPVax) has the potential to elicit a robust adaptive immune response.

Bioinformatics analysis to design a multi-epitope mRNA vaccine against S. agalactiae exploiting pathogenic proteins

Antibiotic resistance in bacterial pathogen infections is a growing global issue that occurs due to their adaptation to changing environmental conditions. Therefore, producing an efficient vaccine as an alternative approach can improve the immune system, eradicate related pathogens, and overcome this growing problem. Streptococcus agalactiae belongs to group B Streptococcus (GBS). Colonization of GBS during pregnancy is a significant risk factor for infants and young children. S. agalactiae infected population exhibits resistance to beta-lactams, including penicillin and the second-line antibiotics erythromycin and clindamycin. On the other hand, there are currently no commercial vaccines against this pathogen. Vaccination of pregnant women is a highly effective method to protect newborns and infants from S. agalactiae infection, and it has been identified as an urgent demand by the World Health Organization. This study employed various immunoinformatic tools to develop an effective vaccine that could trigger both humoral and cell-mediated immunity and prevent disease. For this purpose, three conserved antigenic proteins of the main pathogenic strains of S. agalactiae were utilized to predict CTL, HTL, and B-cell epitopes for producing an mRNA vaccine against different strains of S. agalactiae. The selected epitopes were fused using proper linkers. The Resuscitation promoting factor E (RpfE) sequence was incorporated in the designed vaccine construct as an adjuvant to boost its immune response. Different physicochemical characteristics of the final designed vaccine, modeling of the three-dimensional structure, molecular docking, molecular dynamics simulation, and immunological response simulation were screened following vaccine administration in an in vivo model. Computational immune simulation data identified that IgG1, IgM, INF γ, IL-2, T helper, and B-cell populations increased significantly after vaccination. These findings suggested that the vaccine candidate may provide good protection against S. agalactiae infection. However, experimental and animal model studies are required for additional validation and implementation in human vaccination programs.

Immunoinformatics investigation on pathogenic Escherichia coli proteome to develop an epitope-based peptide vaccine candidate.

Escherichia coli (E. coli), a gram-negative bacterium, quickly colonizes in the human gastrointestinal tract after birth and typically sustains a long-term, symbiotic relationship with the host. However, certain virulent strains of E. coli can cause diseases such as urinary tract infections, meningitis, and enteric disorders. The rising antibiotic resistance among these strains has heightened the urgency for an effective vaccine. This study employs immunoinformatics and a reverse vaccinology technique to identify prospective antigens and create an efficient vaccine construct. In this study, we reported the "Attaching and Effacing Protein" a novel outer-membrane protein conserved in all pathogenic E. coli strains, based on proteome screening. We developed an in silico multi-epitope vaccine that includes helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), B cell lymphocyte (BCL), and pan HLA DR-binding reactive epitope (PADRE) sequences, along with appropriate linkers and adjuvants. Machine Learning algorithms were used to evaluate antigenicity, solubility, stability, and non-allergenicity of the vaccine construct. Additionally, molecular docking analysis revealed that vaccine construct has a strong predicted binding affinity for human toll-like receptors on the cell surface. In this context, laboratory validations are necessary to demonstrate the effectiveness of the possible vaccine design that showed encouraging findings through computational validation.

Rapid and efficient immune response induced by a designed modular cholera toxin B subunit (CTB)-based self-assembling nanoparticle

Modular self-assembling nanoparticle vaccines, represent a cutting-edge approach in immunology with the potential to revolutionize vaccine design and efficacy. Although many innovative efficient modular self-assembling nanoparticles have been designed for vaccination, the immune activation characteristics underlying such strong protection remain poorly understood, limiting the further expansion of such nanocarrier. Here, we prepared a novel modular nanovaccine, which self-assembled via a pentamer cholera toxin B subunit (CTB) domain and an unnatural trimer domain, presenting S. Paratyphi A O-polysaccharide antigen, and investigated its rapid immune activation mechanism. The nanovaccine efficiently targets draining lymph nodes and antigen-presenting cells, facilitating co-localization with Golgi and endoplasmic reticulum. In addition, dendritic cells, macrophages, B cells, and neutrophils potentially participate in antigen presentation, unveiling a dynamic change of the vaccines in lymph nodes. Single-cell RNA sequencing at early stage and iN vivo/iN vitro experiments reveal its potent humoral immune response capabilities and protection effects. This nanoparticle outperforms traditional CTB carriers in eliciting robust prophylactic effects in various infection models. This work not only provides a promising and efficient candidate vaccine, but also promotes the design and application of the new type of self-assembled nanoparticle, offering a safe and promising vaccination strategy for infection diseases.

“I’d just love to hear what the community has to say”: Exploring the potential of community-driven vaccine messaging amongst ethnic minority communities

ABSTRACT Community-based communication interventions improve health outcomes and foster positive behavioral changes across diverse populations. However, their potential to support vaccine readiness remains underexplored. This paper addresses this gap by investigating the opinions and preferences of ethnic minority community members who attended a health information session regarding community-delivered vaccine messaging. The study explored the perceptions and willingness to engage in community-led communication efforts about vaccination, focusing on COVID-19 booster vaccines. In-depth interviews were conducted between November and December 2023 with individuals from ethnic minority communities in Central Eastern Sydney who attended an information session about COVID-19 boosters. Four key themes emerged from speaking to this specific group, highlighting diverse communication preferences and intentions. Participants emphasized obtaining vaccine-related knowledge from various sources, particularly through interpersonal discussions. Trusted voices like general practitioners (GPs) and targeted media campaigns were deemed to be crucial. Recommendations included leveraging community champions and establishing a central body for efficient vaccination campaign management in multicultural communities. Personal engagement through community discussions was stressed, with inclusive spaces recommended in various settings. Effective strategies include transparent communication, credible health professional endorsement, and addressing concerns with balanced responses. The findings accentuate the potential effectiveness of grassroots, community-centric initiatives in promoting informed vaccine messaging, countering misinformation, and engaging communities in meaningful health dialogs. Further research on tailored communication and strategic partnerships could enhance this initiative and promote sustained health literacy within ethnic minority communities.

Immune enhancement of rhamnolipid/manganese calcium phosphate mineralized nanoparticle: A promising subunit antigen delivery system

The use of biomimetic mineralization strategy is promising to solve the problem of poor stability and immune effect of subunit antigens. However, non-specifically inducing protein mineralization is still a challenge. we hypothesized that rhamnolipids with both protein and metal binding capacity could be used to develop more functional and biocompatible calcium mineralized nanoparticle (RMCP). The results show that rhamnolipids synergistically enhanced the mineralization of protein with manganese ions and improved 21 % the loading antigens of RMCP compared to manganese calcium phosphate nanoparticles. Transmission electron microscopy (TEM) and Dynamic Light Scattering (DLS) showed particle size of RMCP is 260 ± 12.1 nm with spherical morphology. In vitro experiments have shown that RMCP effectively activate immune cells through the cGAS-STING and NLRP3 pathways and demonstrated a higher level of cytokines in RAW264.7 Macrophages. In vivo, RMCP triggered an increased IgG titer with 16.5-fold IgG2a/IgG1 ratio compared to the aluminum adjuvant which improved the recovery status after challenge in mice. We used biological surfactants for the first time to enhance the biomimetic mineralization process of subunit antigen, which provides a new approach for constructing calcium-based biocompatible antigen delivery vectors, helping to develop a new generation of stable, efficient, and safe subunit vaccines.

Designing of potential siRNA molecules for African norovirus gene silencing: A computational approach

Introducing siRNAs into cells could degrade specific messenger RNA (mRNA) molecules, reducing the expression of the corresponding protein encoded by those mRNA molecules. Norovirus is the leading cause of both epidemic and pandemic acute gastroenteritis, which is inflammation of the stomach and intestine worldwide, and, as of present, no efficient vaccine is available to combat this norovirus disease. Since siRNA, therapeutics have gained significant attention for their potential to target and silence disease-causing genes. Our study utilizes different computational tools to design siRNA agents against the polyprotein of norovirus without causing off-target effects. According to the results of GC (guanine-cytosine) content, fold-free energy, binding energy, melting temperature, efficacy predictions, and molecular docking against human argonaute 2 protein (AGO2), two siRNA molecules are expected to exert the most effective action. The effectiveness and efficiency of siRNAs against norovirus need to be further examined in vivo before their use as alternative and practical molecular therapeutic agents.

New insights for the development of efficient DNA vaccines.

Despite the great potential of DNA vaccines for a broad range of applications, ranging from prevention of infections, over treatment of autoimmune and allergic diseases to cancer immunotherapies, the implementation of such therapies for clinical treatment is far behind the expectations up to now. The main reason is the poor immunogenicity of DNA vaccines in humans. Consequently, the improvement of the performance of DNA vaccines invivo is required. This mini-review provides an overview of the current state of DNA vaccines and the various strategies to enhance the immunogenic potential of DNA vaccines, including (i) the optimization of the DNA construct itself regarding size, nuclear transfer and transcriptional regulation; (ii) the use of appropriate adjuvants; and (iii) improved delivery, for example, by careful choice of the administration route, physical methods such as electroporation and nanomaterials that may allow cell type-specific targeting. Moreover, combining nanoformulated DNA vaccines with other immunotherapies and prime-boost strategies may help to enhance success of treatment.

A Nanobody-based TRIM-away targets the intracellular protein degradation of African swine fever virus

African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a hemorrhagic illness with high fatality rates in domestic pigs that has resulted in a substantial socio-economic loss and threatens the global pork industry. Very few safe and efficient vaccines or compounds against ASF are commercially available, thus developing new antiviral strategies is urgently required. Targeted protein degradation (TPD) has emerged as one of the most innovative strategies for drug discovery. In this study, we generate Nanobody-based TRIM-aways specifically binding with and targeting ASFV-encoded structural proteins p30, p54, and p72 for degradation. Furthermore, nanobody-based trim-aways exhibit robust viral structural protein degradation capabilities in ASFV-infected iPAM and MA104 cells through both proteasomal and lysosomal pathways, concurrently demonstrating potent anti-ASFV activity with less viral production. Our study highlights the Nanobody-based TRIM-away targeting viral protein degradation as a potential candidate for the development of a novel antiviral strategy against ASF.

Artificial Intelligence in public health: A case study

Artificial Intelligence technology has become an innovative tool in global healthcare that helps to manage various problems of scale and complexity. Its use in public health is multifaceted and multivariate extending across early outbreak detection, risk modeling and prediction, efficient vaccine logistics and administration, reducing health disparities, aiding assist in diagnosis, everyday monitoring of chronic diseases, telemedicine and virtual chatbots especially for elderly care, mental health and oncology patients, and community engagement. Despite these huge generational advantages, multiple challenges exist in data quality, security and misuse, individual privacy, contextual application, accountability and oversight and remain primary concerns for universal adoption of artificial intelligence. There is a need for safeguards and a global regulatory framework to responsibly harvest the benefits of artificial intelligence for the advancement of public and community health.

In Silico Development of a Multi-Epitope Subunit Vaccine against Bluetongue Virus in Ovis aries Using Immunoinformatics.

The bluetongue virus (BTV), transmitted by biting midges, poses a significant threat to livestock globally. This orbivirus induces bluetongue disease, leading to substantial economic losses in the agricultural sector. The current control measures have limitations, necessitating the development of novel, efficient vaccines. In this study, an immunoinformatics approach is employed to design a multi-epitope subunit vaccine for Ovis aries targeting six BTV serotypes. Focusing on the VP2 capsid protein, the vaccine incorporates B-cell, helper-T lymphocytes (HTL), and cytotoxic T-cell lymphocytes (CTL) epitopes. Molecular docking reveals stable interactions with TLR2 and TLR4 receptors, suggesting the stability of the complex, indicating the potential viability of the multi-epitope vaccine. The computational approach offers a rapid and tailored strategy for vaccine development, highlighting potential efficacy and safety against BTV outbreaks. This work contributes to understanding BTV and presents a promising avenue for effective control.

Improving the last mile delivery of vaccines through an informed push model: Experiences, opportunities and costs based on an implementation study in a rural district in Uganda.

Developing countries face challenges in ensuring equitable, timely, and efficient vaccine availability at health facilities. In Uganda, the distribution of vaccines from district stores to the last-mile health facilities is hindered by an unpredictable and unreliable mixed push-pull delivery system. This system often results in poor vaccine management, stock-outs, and missed vaccination opportunities. This pilot study aimed to enhance the efficiency of last-mile vaccine delivery by implementing an informed push model. The specific goals were to improve vaccine lead time, standardize cold chain management during transportation, and evaluate the costs of implementing the informed push model. A mixed methods approach was used to evaluate the impact of the informed push model in Gomba district, Uganda. Both quantitative and qualitative data were collected at baseline and endline. Quantitative data included mode, frequency, lead-time, and costs of vaccine delivery, vaccine stock status, and cold chain maintenance during transportation, gathered through semi-structured interviews. Qualitative data on experiences and challenges were collected using a guide. Descriptive statistics were used for quantitative data analysis, while an ingredients approach was used for costing data. Thematic analysis was applied to qualitative data. The informed push system significantly improved vaccine delivery efficiency and quality in Gomba district. The average lead-time for vaccine delivery reduced from 14 days at baseline to 5 days at endline. Timely vaccine receipt at health facilities increased from 36.8% to 100%. Temperature monitoring during transit improved from 26.3% to 100%. The proportion of facilities experiencing stock-outs dropped from 79.0% to 36.8%. Monthly distribution costs decreased from $494.8 ($0.07 per child) to $445.9 ($0.06 per child). The informed push model is a cost-effective strategy for improving last-mile vaccine delivery by reducing lead times, enhancing cold chain management, and decreasing stock-outs. Integration into the national immunization program is recommended for broader adoption in Uganda.

A vaccine candidate based on baculovirus displaying chikungunya virus E1-E2 envelope confers protection against challenge in mice.

Chikungunya fever is a re-emerging mosquito-borne disease caused by the chikungunya virus (CHIKV) and produces acute arthritis that can progress to chronic disease with arthralgia. The first approved live-attenuated chikungunya vaccine has only recently become available for use in humans in the USA, but the access in endemic regions remains unmet. Here, we exploited the baculovirus display technology to develop a vectored vaccine candidate that exposes the CHIKV membrane proteins E1 and E2 on the baculovirus surface. Using recombinant baculovirus as vector vaccines has both productive and regulatory advantages: they are safe for handling and easy to produce in high titers and are non-pathogenic and non-replicative in mammals but have strong adjuvant properties by inducing humoral and cellular immune responses. CHIKV E1 and E2 envelope proteins with their own signal and transmembrane sequences were expressed on the surface of budded baculovirus virions. Immunization of C57BL/6 mice with non-adjuvanted recombinant baculovirus induced IgG antibodies against E2 with a predominant IgG2c subtype, neutralizing antibodies and a specific IFN-γ CD8+ T-cell response. Immunization with a second dose significantly boosted the antibody response, and mice immunized with two doses of the vaccine candidate were completely protected against challenge with CHIKV showing no detectable viremia or signs of disease. Altogether, baculovirus display of CHIKV envelope proteins served as an efficient vaccine platform against CHIKV.IMPORTANCEThe global spread of chikungunya virus (CHIKV) has disproportionately impacted the Americas that experienced a fourfold increase in 2023 in cases and deaths compared with the same period in 2022. The disease is characterized by acute fever and debilitating joint pain that can become chronic. Despite the socioeconomic burden related to the high morbidity rates of CHIKV infection, a vaccine for CHIKV is currently approved only in the USA. Vaccines are the most effective preventive measure against viral diseases, and advances in the development of different vaccine platforms such as nucleic acids and viral vectors have prompted the rapid deployment of vaccines to contain the COVID-19 pandemic. Here, we report the use of baculovirus display as a strategy for the design of a novel vaccine that provides sterilizing immunity in a mouse model of chikungunya disease. Our results encourage further research regarding the potential of baculovirus as platforms for human vaccine design.

Application of Controlled Release Mechanisms in Vaccine Delivery

Vaccines, as an essential means of preventive medicine, profoundly impact human health by stimulating an immune response to protect the body from pathogens or treat diseases. However, conventional vaccine delivery methods have limitations such as multiple injections, rapid degradation in vivo, and difficulty in targeted delivery. The development of controlled release mechanisms has overcome these challenges, optimized the immune response and improved the efficacy and safety of vaccines by precisely controlling the time, space and dose of vaccine release in vivo. This review explores the fundamentals, recent applications and future directions of controlled release mechanisms in vaccine delivery, focusing on the design and application of intelligent delivery systems such as biodegradable nanoparticles, self-healing microspheres, scaffolded vaccines and targeted vaccine systems. With the continuous progress of biotechnology and nanotechnology, controlled-release vaccines herald a new direction in vaccine design and delivery and bring efficient vaccine products to global public health.

Attenuated African swine fever viruses and the live vaccine candidates: a comprehensive review.

The African swine fever virus (ASFV) is spreading worldwide and causing huge economic losses to the global pig industry. The ASFV genome is 170-193 kb in length, contains approximately 150 open reading frames, and encodes more than 200 proteins, most of which have unknown functions. Owing to the unique viral structure, replication strategy, large number of genes of unknown function, and complicated pathogenesis, vaccine development research is challenging. Several naturally attenuated ASFV isolates have been extensively investigated and many genetically manipulated, gene-deleted, and cell-adapted ASFVs have been reported. Currently, live attenuated viruses prepared from weakly virulent strains are an efficient method to provide effective protection in vaccinated pigs; however, these have seldom been widely approved for vaccine use, except in Vietnam. Herein, we summarize the attenuated isolates or vaccine candidates for live vaccines derived from different sources, including naturally mutated, attenuated, cell-adapted, and genetically modified recombinant ASFVs. This will help to understand the gene function and immunogenicity of attenuated live ASFV, as well as the shortcomings of these viruses as vaccine candidates, and provide clues to prepare live, efficient, and safe vaccines for African swine fever.IMPORTANCEOutbreaks of African swine fever (ASF) have caused devastating losses to the global pig industry. Pigs immunized with ASFV attenuated virus can resist the lethal challenge of a strongly virulent virus. Here, we summarize the virulence of naturally mutated, cell-adapted, and genetically recombinant ASFV for pigs, and the protective effect after facing an attack challenge. We also analyze the advantages and disadvantages of ASFV attenuated viruses as vaccine candidates to provide clues for the preparation of efficient and safe live African swine fever vaccines.

Transcutaneous Immunization of 1D Rod-Like Tobacco-Mosaic-Virus-Based Peptide Vaccine via Tip-Loaded Dissolving Microneedles.

Peptide vaccines induce specific neutralizing antibodies and are effective in disease prevention and treatment. However, peptide antigens have a low immunogenicity and are unstable, requiring efficient vaccine carriers to enhance their immunogenicity. Here, we develop a tobacco mosaic virus (TMV)-based peptide vaccine for transdermal immunization using a tip-loaded dissolving microneedle (MN) patch. TMV is decorated with the model peptide antigen PEP3. The prepared TMV-PEP3 promotes dendritic cell maturation and induces dendritic cells to overexpress MHC II, costimulatory factors, and pro-inflammatory factors. By encapsulation of TMV-PEP3 in the tips of a trehalose MN, TMV-PEP3 can be delivered by MN and significantly promote local immune cell infiltration. In vivo studies show that both subcutaneous injection and MN administration of TMV-PEP3 increase the production of anti-PEP3 IgG antibodies and the harvested serum can induce complement-dependent cytotoxicity. This work provides a promising strategy for constructing efficient and health-care-friendly peptide vaccines.

A guide to global access to HPV vaccination to all women in low- and middle-income countries; a minireview of innovation and equity.

Cervical cancer is caused by the human papillomavirus (HV), and accounts for more than 311,000 preventable deaths annually, with 85% occurring in low-and middle-income countries. Despite being preventable through screening and screening, significant barriers to implementing HPV vaccination persist in developing nations. This review study aims to identify these barriers and propose innovative, evidence-based solutions to improve vaccination rates and reduce cervical cancer mortality. A systematic review search was conducted using PubMed, Embase, and Cochrane Database of Systemic Reviews. Keywords related to HPV vaccination barriers and implementation strategies in developing countries were used. Relevant demonstration projects, pilot studies, and evidence-based research articles were reviewed. Identifiable barriers to a successful vaccine implementation program in a developing country include vaccine costs, societal, cultural resistance, misinformation, logistical challenges in vaccine delivery, and inadequate human resources. Solutions to these barriers include a subsidized vaccine pricing, community sensitization, education and well-trained media professionals to dispel misinformation, and partnerships with both public and private sector for efficient vaccine distribution. These findings highlight critical barriers that impede HPV vaccination efforts in developing countries and offers practical solutions to overcome these challenges. This aggregate of data can help inform future developing countries' implementation programs to further the World Health Assembly mission to vaccinate 90% of eligible girls globally by 2030.

HPV16 mutant E6/E7 construct is protective in mouse model

BackgroundHuman papillomavirus type 16 (HPV-16) infection is strongly associated with considerable parts of cervical, neck, and head cancers. Performed investigations have had moderate clinical success, so research to reach an efficient vaccine has been of great interest. In the present study, the immunization potential of a newly designed HPV-16 construct was evaluated in a mouse model.ResultsInitially, a construct containing HPV-16 mutant (m) E6/E7 fusion gene was designed and antigen produced in two platforms (i.e., DNA vaccine and recombinant protein). Subsequently, the immunogenicity of these platforms was investigated in five mice) C57BL/6 (groups based on several administration strategies. Three mice groups were immunized recombinant protein, DNA vaccine, and a combination of them, and two other groups were negative controls. The peripheral blood mononuclear cells (PBMCs) proliferation, Interleukin-5 (IL-5) and interferon-γ (IFN-γ) cytokines, IgG1 and IgG2a antibody levels were measured. After two weeks, TC-1 tumor cells were injected into all mice groups, and subsequently further analysis of tumor growth and metastasis and mice survival were performed according to the schedule.Overall, the results obtained from in vitro immunology and tumor cells challenging assays indicated the potential of the mE6/E7 construct as an HPV16 therapeutic vaccine candidate. The results demonstrated a significant increase in IFN-γ cytokine (P value < 0.05) in the Protein/Protein (D) and DNA/Protein (E) groups. This finding was in agreement with in vivo assays. Control groups show a 10.5-fold increase (P value < 0.001) and (C) DNA/DNA group shows a 2.5-fold increase (P value < 0.01) in tumor growth compared to D and E groups. Also, a significant increase in survival of D and E (P value < 0.001) and C (P value < 0.01) groups were observed.ConclusionsSo, according to the findings, the recombinant protein could induce stronger protection compared to the DNA vaccine form. Protein/Protein and DNA/Protein are promising administration strategies for presenting this construct to develop an HPV-16 therapeutic vaccine candidate.

TEMPORAL AND SPATIAL MODELING OF THE SPREAD OF DENGUE FEVER IN BRAZIL

Dengue is a viral infection caused by an arbovirus and spread through the bites of mosquitoes of the genus Aedes which causes significant human and economic damage every year. Preventive measures have been taken to reduce the proliferation of the transmitting mosquito and efforts are being made to obtain an efficient vaccine for the disease. Parallel to these measures, several studies present a model for the spread of the disease in order to determine relevant factors in the process and thus guide preventive measures and future vaccination initiatives. Within this context, this work brings a modeling for the spread of the disease through a system of differential equations where the geographic region studied (a Brazilian city) is divided into sub-regions with human circulation between them, thus making humans the spreader of the disease. Using the model, it was possible to characterize the time series of people infected with dengue in the city of Goiânia, Brazil, between 2000 and 2003 using two and three subdivisions of the geographic region studied. Seasonal cycles of the disease have been described without exhausting the number of susceptible humans.

An intranasal cationic liposomal polysaccharide vaccine elicits humoral immune responses against Streptococcus pneumoniae

Diseases caused by S. pneumoniae are the leading cause of child mortality. As antibiotic resistance of S. pneumoniae is rising, vaccination remains the most recommended solution. However, the existing pneumococcal polysaccharides vaccine (Pneumovax® 23) proved only to induce T-independent immunity, and strict cold chain dependence of the protein conjugate vaccine impedes its promotion in developing countries, where infections are most problematic. Affordable and efficient vaccines against pneumococcus are therefore in high demand. Here, we present an intranasal vaccine Lipo+CPS12F&αGC, containing the capsular polysaccharides of S. pneumoniae 12F and the iNKT agonist α-galactosylceramide in cationic liposomes. In BALB/cJRj mice, the vaccine effectively activates iNKT cells and promotes B cells maturation, stimulates affinity-matured IgA and IgG production in both the respiratory tract and systemic blood, and displays sufficient protection both in vivo and in vitro. The designed vaccine is a promising, cost-effective solution against pneumococcus, which can be expanded to cover more serotypes and pathogens.