Enhance Vaccine Efficacy Research Articles

Exploring yeast glucans for vaccine enhancement: Sustainable strategies for overcoming adjuvant challenges in a SARS-CoV-2 model.

Vaccine adjuvants are important for enhancing vaccine efficacy, and although aluminium salts (Alum) are the most used, their limited ability to induce specific immune responses has spurred the search for new adjuvants. However, many adjuvants fail during product development due to manufacturability, supply, stability, or safety concerns. This work hypothesizes that protein-free yeast glucans can be used as vaccine adjuvants due to their known immunostimulatory activity and high abundancy. Thus, high molecular weight glucans with over 99% purity, comprising 64-70% β-glucans and 29-35% α-glucans, were extracted from a wild-type yeast and an engineered yeast to produce a steviol glycoside. These glucans underwent carboxymethylation to enhance solubility. Both water-dispersible and particulate glucans were evaluated as adjuvants, either alone or in combination with Alum or squalene stable emulsion (SE), for a SARS-CoV-2 vaccine. The study demonstrated that glucans triggered a robust immune response and enhanced the effects of Alum and SE when used in combination, both in vitro and in vivo. Water-dispersible glucans combined with Alum, and particulate glucans combined with SE, increased the production of specific antibodies against SARS-CoV-2 spike protein and enhanced serum neutralization titers against SARS-CoV-2 pseudovirus. Furthermore, the results indicated that larger molecular weight glucans from engineered yeast exhibited stronger immunogenic activity in comparison to wild-type yeast glucans. In conclusion, appropriately formulated glucans have the potential to be scalable, low-cost vaccine adjuvants, potentially overcoming the limitations of current adjuvants.

A novel neuro-attenuated vaccine candidate with excellent safety and protective efficacy against highly virulent Feline Herpesvirus-1

Feline herpesvirus 1 (FHV-1) is a major pathogen responsible for respiratory, ocular and nervous system symptoms in felines. FHV-1 can remain latenct in ganglia and is difficult to eliminate completely with drug treatment. Currently, commercially FHV-1 vaccines are not sufficiently effective and provide only limited durations of protection. To enhance vaccine efficacy and reduce latent virus in tissues, two gene deletion mutants of FHV-1 conveyed excellent proliferation ability, genetic stability and attenuated FHV-1 virulence were constructed by CRISPR/Cas9-mediated homologous recombination, designated as FHV-△US3 and FHV-△UL50. Recombinant FHV-1 induce stronger cellular and humoral immune responses, as well as better protective effects than those of commercial vaccines. Notably, FHV-△US3 and FHV-△UL50 reveal neuro-attenuated, as viral residue in the trigeminal ganglia are significantly reduced. The knockout of the UL50 gene in FHV-1 has not been previously reported. In this study, we aimed to evaluate the safety and immunogenicity of FHV-△UL50, highlighting its potential as a novel neuroattenuated vaccine candidate.

Enhancing vaccine efficacy: Evaluating the superiority of cationic liposome-embedded squalene adjuvant against PCV2 infection

Cationic liposome-embedded squalene (CLS) is a promising adjuvant that enhances antigen stability and mobility and improves immune response. This study compares the efficacy of a CLS-adjuvant porcine circovirus type 2 (PCV2) vaccine (CSV) with a conventional vaccine against PCV2. The CSV vaccine showed superior stability and was effective against PCV2-induced growth decline. It significantly increased serum immunoglobulin and cytokine levels, reduced serum PCV2 DNA, shortened the duration of viremia, and provided robust protection. CSV outperformed conventional vaccines, highlighting its potential for innovative vaccine development.

Identifying Plasmodium P36 and P52 antigens for co-administration with circumsporozoite protein to enhance vaccine efficacy.

Vaccines targeting the complex pre-erythrocytic stage of Plasmodium parasites may benefit from inclusion of multiple antigens. However, discerning protective effects can be difficult because newer candidates may not be as protective as leading antigens like the circumsporozoite protein (CSP) in the conventional pre-clinical mouse model. We developed a modified mouse model challenge strategy that maximizes the contribution of T cells induced by novel candidate antigens at the sporozoite challenge time point and used this approach to test Plasmodium P36 and P52 vaccine candidates alone and in concert with non-protective doses of CSP. Co-administration of P36 and/or P52 with CSP achieved 80-100% sterile protection in mice, compared to only 7-30% protection for each individual antigen. P36 and P52 vaccination induced murine CD4+ and CD8+ T cell responses, but not antibody responses. This study adds P36 and P52 as promising vaccine antigens that may enhance protection achieved by CSP vaccination.

From ancient remedies to modern miracles: tracing the evolution of vaccines and their impact on public health.

This review traces the development of vaccines from ancient times to the present, highlighting major milestones and challenges. It covers the significant impact of vaccines on public health, including the eradication of diseases such as smallpox and the reduction of others such as polio, measles, and influenza. The review provides an in-depth look at the COVID-19 vaccines, which were developed at unprecedented speeds due to the urgent global need. The study emphasizes the ongoing potential of vaccine development to address future global health challenges, demonstrating the critical role vaccines play in disease prevention and public health. Moreover, it discusses the evolution of vaccine technology, from live-attenuated and inactivated vaccines to modern recombinant and mRNA vaccines, showcasing the advancements that have enabled rapid responses to emerging infectious diseases. The review underscores the importance of continued investment in research and development, global collaboration, and the adoption of new technologies to enhance vaccine efficacy and coverage. By exploring historical and contemporary examples, the article illustrates how vaccines have transformed medical practice and public health outcomes, providing valuable insights into future directions for vaccine innovation and deployment.

Favourable humoral but reduced cellular immune response to COVID-19 mRNA BNT162b2 vaccine in patients with childhood-onset systemic lupus erythematosus

ObjectiveTo evaluate both humoral and cellular immune responses to the COVID-19 messenger RNA (mRNA; BNT162b2) vaccine in patients with childhood-onset SLE (cSLE) compared with healthy controls and patient controls (kidney...

Enhanced immune response with baculovirus-expressed BoHV-1 glycoprotein D in vaccine development

Bovine herpesvirus 1 (BoHV-1), a significant pathogen in the alpha-herpesvirus subfamily, primarily infects cattle and causes the upper respiratory disease known as infectious bovine rhinotracheitis (IBR). In silico studies evaluated the BoHV-1 D protein to be non-allergenic, non-toxic, and highly antigenic, highlighting its potential as an antigen for vaccine development. Therefore, this study aimed to evaluate the efficacy of a subunit vaccine using the ectodomain of glycoprotein D (gD34–380) as an antigen. The truncated gD was successfully cloned and expressed in both Escherichia coli (E. coli, termed EgD) and baculovirus (termed BgD) systems, with expected molecular weights of 65 kDa and 50 kDa, respectively. For the vaccine formulation, the gD proteins were used either alone or in combination with in-house inactivated BoHV-1. Vaccination of mice and bovines showed that baculovirus-expressed gD34–380 accelerated the antibody response. Moreover, the BgD-vaccinated group also showed significantly higher neutralizing antibody levels against BoHV-1 than the control group (p<0.0001). In conclusion, our study found that BgD from BoHV-1 can increase the immune response and enhance vaccine efficacy.

The gut microbiota modifies antibody durability and booster responses after SARS-CoV-2 vaccination

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are pivotal in combating coronavirus disease 2019 (COVID-19); however, the declining antibody titers postvaccination pose challenges for sustained protection and herd immunity. Although gut microbiome is reported to affect the early antibody response after vaccination, its impact on the longevity of vaccine-induced antibodies remains unexplored.MethodsA prospective cohort study was conducted involving 44 healthy adults who received two doses of either the BNT162b2 or ChAdOx1 vaccine, followed by a BNT162b2 booster at six months. The gut microbiome was serially analyzed using 16S rRNA and shotgun sequencing, while humoral immune response was assessed using a SARS-CoV-2 spike protein immunoassay.ResultsFaecalibacterium prausnitzii was associated with robust and persistent antibody responses post-BNT162b2 vaccination. In comparison, Escherichia coli was associated with a slower antibody decay following ChAdOx1 vaccination. The booster immune response was correlated with metabolic pathways involving cellular functions and aromatic amino acid synthesis.ConclusionsThe findings of this study underscored the potential interaction between the gut microbiome and the longevity/boosting effect of antibodies following vaccination against SARS-CoV-2. The identification of specific microbial associations suggests the prospect of microbiome-based strategies for enhancing vaccine efficacy.

KLF2 determines the susceptibility of T cells to immunoregulatory NK cells.

Natural killer (NK) cells suppress cellular and humoral immune responses via killing of T cells, resulting in diminished vaccine responses in mice and humans. Efforts to overcome this roadblock and achieve optimal immunity require an improved understanding of the molecular mediators facilitating NK cell-targeting of discrete subsets of CD4 T cells. We employed single-cell forensic victimology and CRISPR-Cas9 editing to delineate a transcriptional program uniquely responsible for the susceptibility of a subpopulation of CD4 T cells to perforin-dependent immunoregulation by NK cells. The unique vulnerability of these CD4 T cells relative to other subsets of CD4 T cells was not associated with a pattern of NK-cell-receptor ligand expression that would favor activation of NK cells. Instead, susceptible CD4 T cells were skewed toward follicular helper T cell (Tfh) differentiation and exhibited intermediate expression of Klf2 and a related suite of KLF2-target genes (e.g. S1pr1) involved in cell migration and spatial positioning. NK-cell dependent suppression of the subset of Tfh exhibiting intermediate expression of KLF2 and S1PR1 was confirmed with single-cell proteomics. CRISPR targeting of KLF2 in CD4 T cells prevented suppression by NK cells. Thus, KLF2 regulation of spatial positioning of T cells is a key determinant of NK-cell immunoregulatory function and a possible target for strategies to enhance vaccine efficacy.

Advancements and Challenges in Peptide-Based Cancer Vaccination: A Multidisciplinary Perspective.

With the continuous advancements in tumor immunotherapy, researchers are actively exploring new treatment methods. Peptide therapeutic cancer vaccines have garnered significant attention for their potential in improving patient outcomes. Despite its potential, only a single peptide-based cancer vaccine has been approved by the U.S. Food and Drug Administration (FDA). A comprehensive understanding of the underlying mechanisms and current development status is crucial for advancing these vaccines. This review provides an in-depth analysis of the production principles and therapeutic mechanisms of peptide-based cancer vaccines, highlights the commonly used peptide-based cancer vaccines, and examines the synergistic effects of combining these vaccines with immunotherapy, targeted therapy, radiotherapy, and chemotherapy. While some studies have yielded suboptimal results, the potential of combination therapies remains substantial. Additionally, we addressed the management and adverse events associated with peptide-based cancer vaccines, noting their relatively higher safety profile compared to traditional radiotherapy and chemotherapy. Lastly, we also discussed the roles of adjuvants and targeted delivery systems in enhancing vaccine efficacy. In conclusion, this review comprehensively outlines the current landscape of peptide-based cancer vaccination and underscores its potential as a pivotal immunotherapy approach.

Advances in the study of LNPs for mRNA delivery and clinical applications.

Messenger ribonucleic acid (mRNA) was discovered in 1961 as an intermediary for transferring genetic information from DNA to ribosomes for protein synthesis. The COVID-19 pandemic brought worldwide attention to mRNA vaccines. The emergency use authorization of two COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, were major achievements in the history of vaccine development. Lipid nanoparticles (LNPs), one of the most superior non-viral delivery vectors available, have made many exciting advances in clinical translation as part of the COVID-19 vaccine and therefore has the potential to accelerate the clinical translation of many gene drugs. In addition, due to these small size, biocompatibility and excellent biodegradability, LNPs can efficiently deliver nucleic acids into cells, which is particularly important for current mRNA therapeutic regimens. LNPs are composed cationic or pH-dependent ionizable lipid bilayer, polyethylene glycol (PEG), phospholipids, and cholesterol, represents an advanced system for the delivery of mRNA vaccines. Furthermore, optimization of these four components constituting the LNPs have demonstrated enhanced vaccine efficacy and diminished adverse effects. The incorporation of biodegradable lipids enhance the biocompatibility of LNPs, thereby improving its potential as an efficacious therapeutic approach for a wide range of challenging and intricate diseases, encompassing infectious diseases, liver disorders, cancer, cardiovascular diseases, cerebrovascular conditions, among others. Consequently, this review aims to furnish the scientific community with the most up-to-date information regarding mRNA vaccines and LNP delivery systems.

Enhancing Vaccine Efficacy and Stability: A Review of the Utilization of Nanoparticles in mRNA Vaccines.

The development of vaccines has entered a new era with the advent of nanotechnology, particularly through the utilization of nanoparticles. This review focuses on the role of nanoparticles in enhancing the efficacy and stability of mRNA vaccines. Nanoparticles, owing to their unique properties such as high surface area, tunable size, and their ability to be functionalized, have emerged as powerful tools in vaccine development. Specifically, lipid nanoparticles (LNPs) have revolutionized the delivery of mRNA vaccines by protecting the fragile mRNA molecules and facilitating their efficient uptake by cells. This review discusses the various types of nanoparticles employed in mRNA vaccine formulations, including lipid-based, polymer-based, and inorganic nanoparticles, highlighting their advantages and limitations. Moreover, it explores the mechanisms by which nanoparticles improve immune responses, such as enhanced antigen presentation and the prolonged release of mRNA. This review also addresses the challenges and future directions in nanoparticle-based vaccine development, emphasizing the need for further research to optimize formulations for broader applications. By providing an in-depth analysis of the current advancements in and potential of nanoparticles in mRNA vaccines, this review aims to shed light on their critical role in combating infectious diseases and improving public health outcomes.

Challenges in the Development of Dengue Vaccine

The development of a dengue vaccine presents numerous challenges, largely due to the complexity of the virus and the human immune response. One of the primary hurdles is Antibody-Dependent Enhancement (ADE), where antibodies from a previous dengue infection can facilitate a more severe secondary infection with a different serotype, exacerbating the disease. Cross-reactivity with other flaviviruses, such as Zika, complicates the immune response further. Additionally, the vaccine must elicit a balanced immune response against all four dengue serotypes, which is difficult to achieve. The role of T follicular helper (TFH) cells in enhancing vaccine efficacy has emerged as a critical area of focus. Efficiently targeting and inducing TFH cells through specific adjuvants could enhance neutralizing antibody production and long-lasting immunity, addressing some of the current vaccine limitations. Despite these challenges, ongoing research and trials continue to advance the field towards a more effective dengue vaccine.

Conjugation of TLR7 and TLR7/8 agonists onto weak protein antigen via versatile oxime ligation for enhanced vaccine efficacy

Protein-based subunit vaccines are weakly immunogenic, and developing self-adjuvanting vaccines with adjuvant conjugated to antigen is a promising approach for generating optimal immune responses. Here, we report a novel adjuvant-protein conjugate vaccine based on versatile oxime ligation technique. Firstly, the adjuvant properties of a series of TLR7 and TLR7/8 small molecule agonists in self-adjuvanting vaccines were systematically compared by coupling them to proteins in consistent ratio via p-carboxybenzaldehyde (p-CBA) for the first time. All conjugate vaccines induced cytokine secretion in murine and human macrophages in vitro, and promoted specific antibody production in vivo. Notably, a conjugate containing imidazoquinoline TLR7/8 agonist (TLR7/8a1) showed the greatest enhancement in Th1/2 balanced antibody response. To minimize the interference with the protein antigenic integrity, we further developed a systematic glycoconjugation strategy to conjugate this TLR7/8a1 onto the glycan chains of SARS-CoV-2 S1 glycoprotein via oxime ligation, in which S1 containing different numbers of aldehyde groups were obtained by differential periodate oxidation. The resulting TLR7/8a1-S1 conjugate triggered a potent humoral and cellular immunity in vivo. Together these data demonstrate the promise of these TLR7 and TLR7/8 agonists as effective built-in adjuvants, and the versatile oxime ligation strategy might broaden potential applications in designing different conjugate vaccines.

Protection efficacy and the safety of the synergy between modified Bazhen powder and PRRSV modified-live virus vaccine against HP-PRRSV in piglets.

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) poses a significant threat to the global swine industry. Vaccination is a preventive measure against viral infections. However, the use of vaccines in livestock healthcare programs faces the challenge of safety and delayed immune responses. Earlier studies have shown the potential of modified Bazhen powder as an immunomodulator with significant biological properties, but its effect on vaccines against HP-PRRSV is yet to be studied. This study elucidated how modified Bazhen powder could improve the safety and efficacy of the conventional PRRSV vaccine by evaluating T-cell responses, antibody levels, clinical symptoms, levels of viremia, organ health, and cytokine production. The results revealed that the oral application of modified Bazhen powder in combination with PRRS vaccination improved both cellular and humoral immunity, accelerated viremia clearance, improved lung injury scores, and reduced viral load in the tonsils. The modified Bazhen powder also effectively reduced inflammatory responses following a PRRSV challenge. These findings further highlight the pharmacological properties of modified Bazhen powder as a potential oral immunomodulatory agent that could enhance vaccine efficacy and ensure broad-spectrum protection against HP-PRRSV in pigs.

Dual nature of type I interferon responses and feedback regulations by SOCS1 dictate malaria mortality

IntroductionType I interferon (IFN-I, IFN-α/β), precisely controlled by multiple regulators, including suppressor of cytokine signaling 1 (SOCS1), is critical for host defense against pathogens. However, the impact of IFN-α/β on malaria parasite infections, beneficial or detrimental, remains controversial. ObjectivesThe contradictory results are suspected to arise from differences in parasite species and host genetic backgrounds. To date, no prior study has employed a comparative approach utilizing two parasite models to investigate the underlying mechanisms of IFN-I response. Moreover, whether and how SOCS1 involves in the distinct IFN-α/β dynamics is still unclear. MethodsHere we perform single-cell RNA sequencing analyses (scRNA-seq) to dissect the dynamics of IFN-α/β responses against P. yoelii 17XL (17XL) and P. berghei ANKA (PbANKA) infections; conduct flow cytometry analysis and functional depletion to identify key cellular players induced by IFN-I; and establish mathematical models to explore the mechanisms underlying the differential IFN-I dynamics regulated by SOCS1. Results17XL stimulates an early protective but insufficient toll-like receptor 7 (TLR7)-interferon regulatory factor 7 (IRF7)-dependent IFN-α/β response, resulting in CD11ahiCD49dhiCD4+ T cell activation to enhance anti-malarial immunity. On the contrary, a late IFN-α/β induction through toll-like receptor 9 (TLR9)-IRF7/ stimulator of interferon genes (STING)- interferon regulatory factor 3 (IRF3) dependent pathways expands programmed cell death protein 1 (PD-1)+CD8+ T cells and impairs host immunity during PbANKA infection. Furthermore, functional assay and mathematical modeling show that SOCS1 significantly suppresses IFN-α/β production via negative feedback and incoherent feed-forward loops (I1-FFL). Additionally, differential activation patterns of various transcriptional factors (TFs) synergistically regulate the distinct IFN-I responses. ConclusionThis study reveals the dual functions of IFN-I in anti-malarial immunity: Early IFN-α/β enhances immune responses against Plasmodium infection by promoting CD11ahiCD49dhiCD4+ T cell, while late IFN-α/β suppresses these response by expanding PD-1+CD8+ T cells. Moreover, both the SOCS1-related network motifs and TFs activation patterns contribute to determine distinct dynamics of IFN-I responses. Hence, our findings suggest therapies targeting SOCS1- or TFs-regulated IFN-I dynamics could be an efficacious approach for preventing malaria and enhancing vaccine efficacy.

Combating Malaria with Vaccines: Insights from the One Health Framework

Malaria remains a leading cause of morbidity and mortality worldwide, with significant efforts directed towards developing effective vaccines to curb its impact. The One Health concept, recognizing the interconnectedness of human, animal, and environmental health, offers a comprehensive approach to understanding and combating this disease. This review examines the development of malaria vaccine through the lens of the One Health framework, highlighting the integration of human, vector, and environmental factors in the fight against malaria. We discuss the current landscape of malaria vaccine development, including the deployment of the RTS,S/AS01 vaccine and the progress of other candidates such as the R21/Matrix-M and PfSPZ vaccine. The challenges posed by the complex lifecycle of the malaria parasite, its genetic diversity, and the environmental factors influencing transmission are explored. This review also discusses emerging technologies and innovations that could enhance vaccine efficacy and delivery. Additionally, we consider ethical, social, and economic factors critical to the successful implementation of vaccination programs. In concluding, this review underscores the importance of adopting a One Health approach to malaria vaccine development, advocating for integrated efforts to address the multifaceted challenges of malaria control and eradication.

A mathematical fractal-fractional model to control tuberculosis prevalence with sensitivity, stability, and simulation under feasible circumstances

Background:Tuberculosis, a global health concern, was anticipated to grow to 10.6 million new cases by 2021, with an increase in multidrug-resistant tuberculosis. Despite 1.6 million deaths in 2021, present treatments save millions of lives, and tuberculosis may overtake COVID-19 as the greatest cause of mortality. This study provides a six-compartmental deterministic model that employs a fractal–fractional operator with a power law kernel to investigate the impact of vaccination on tuberculosis dynamics in a population. Methods:Some important characteristics, such as vaccination and infection rate, are considered. We first show that the suggested model has positive bounded solutions and a positive invariant area. We evaluate the equation for the most important threshold parameter, the basic reproduction number, and investigate the model’s equilibria. We perform sensitivity analysis to determine the elements that influence tuberculosis dynamics. Fixed-point concepts show the presence and uniqueness of a solution to the suggested model. We use the two-step Newton polynomial technique to investigate the effect of the fractional operator on the generalized form of the power law kernel. Results:The stability analysis of the fractal–fractional model has been confirmed for both Ulam–Hyers and generalized Ulam–Hyers types. Numerical simulations show the effects of different fractional order values on tuberculosis infection dynamics in society. According to numerical simulations, limiting contact with infected patients and enhancing vaccine efficacy can help reduce the tuberculosis burden. The fractal–fractional operator produces better results than the ordinary integer order in the sense of memory effect at diffract fractal and fractional order values. Conclusion:According to our findings, fractional modeling offers important insights into the dynamic behavior of tuberculosis disease, facilitating a more thorough comprehension of their epidemiology and possible means of control.

Functionalized chitosan-G-poly caprolactone vaccine delivery system fabricated to display antigen–antibody immune complexes of Mycobacterium tuberculosis elicits immune response in Ex-vivo model

BackgroundVaccine development against tuberculosis remains a global health imperative, necessitating robust immunogenicity and safety profiles. Nanoparticle-based delivery systems offer promising avenues to enhance vaccine efficacy while ensuring tolerability. This study explores the utilization of chitosan micelles as a delivery platform for immune complex vaccination against tuberculosis. Leveraging two key antigens of Mycobacterium tuberculosis, namely HspX and Mpt51, known for their relevance in latent tuberculosis and its co-infection with the human immunodeficiency virus, immune complexes were synthesized in vitro using antibodies raised against these antigens. The immune complexes were then conjugated onto chitosan micelles, characterized for their physicochemical properties, and evaluated for their biocompatibility and immunogenicity.ResultsChitosan nanoparticles conjugated with either antigen or its immune complexes were synthesized as micelles and physicochemical characterizations confirm the formation of micelles without altering the polymer composition. These immune complex-conjugated chitosan micelles were found to be safe, exhibiting no significant hemolytic and cytotoxic activity even at a higher concentration of 400 µg/ml. Peripheral blood mononuclear cells upon stimulation with immune complex-conjugated chitosan micelles showed enhanced cellular uptake and one to two-fold increased expression of key immune markers—interferon gamma and CD-86.ConclusionsThese findings underscore the potential of chitosan nanoparticles as a versatile delivery platform for immune complex vaccination against tuberculosis. While limitations exist, such as including only two markers of immune modulation, this study lays a foundation for future investigations into immune complex vaccine potential in animal models. In conclusion, chitosan micelles carrying immune complexes of HspX and Mpt51 tuberculosis antigens exhibit promising immunogenicity, highlighting their potential as a platform for multi-antigenic vaccine components warranting further in vivo studies.

Lipid Nanoparticle with 1,2-Di-O-octadecenyl-3-trimethylammonium-propane as a Component Lipid Confers Potent Responses of Th1 Cells and Antibody against Vaccine Antigen.

Adjuvants are effective tools to enhance vaccine efficacy and control the type of immune responses such as antibody and T helper 1 (Th1)- or Th2-type responses. Several studies suggest that interferon (IFN)-γ-producing Th1 cells play a significant role against infections caused by intracellular bacteria and viruses; however, only a few adjuvants can induce a strong Th1-type immune response. Recently, several studies have shown that lipid nanoparticles (LNPs) can be used as vaccine adjuvants and that each LNP has a different adjuvant activity. In this study, we screened LNPs to develop an adjuvant that can induce Th1 cells and antibodies using a conventional influenza split vaccine (SV) as an antigen in mice. We observed that LNP with 1,2-di-O-octadecenyl-3-trimethylammonium-propane (DOTMA) as a component lipid (DOTMA-LNP) elicited robust SV-specific IgG1 and IgG2 responses compared with SV alone in mice and was as efficient as SV adjuvanted with other adjuvants in mice. Furthermore, DOTMA-LNPs induced robust IFN-γ-producing Th1 cells without inflammatory responses compared to those of other adjuvants, which conferred strong cross-protection in mice. We also demonstrated the high versatility of DOTMA-LNP as a Th1 cell-inducing vaccine adjuvant using vaccine antigens derived from severe acute respiratory syndrome coronavirus 2 and Streptococcus pneumoniae. Our findings suggest the potential of DOTMA-LNP as a safe and effective Th1 cell-inducing adjuvant and show that LNP formulations are potentially potent adjuvants to enhance the effectiveness of other subunit vaccines.