Potent Cellular Immune Responses Research Articles

Chinese yam polysaccharide-loaded aluminium hydroxide nanoparticles used as vaccine adjuvant to induce potent humoral and cellular immune responses

Due to their safety and efficacy, aluminium salts (Alum) are considered the most important adjuvants in human vaccines. However, Alum adjuvants are unable to elicit a cellular immune response, which is vital for the prevention of various chronic infectious diseases and cancers. Herein, we isolated and purified a water-soluble polysaccharide from Chinese yam, named CYP, which was primarily composed of →4)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, and α-D-Glcp-(1→. Meanwhile, we prepared aluminium hydroxide nanoparticles (Al NPs) with a nanometer-scale size and thin stick-like shape. Being an immunostimulant, the CYP was then loaded onto the Al NPs to obtain a novel adjuvant delivery system (CYP-Al NPs) that enhances the immunostimulatory activity of CYP. Our findings showed that the CYP-Al NPs facilitated macrophages activation and promoted the antigen uptake by macrophages. The in vivo experiment showed that the CYP-Al NPs, as the adjuvant to ovalbumin, promoted the activation of dendritic cells and germinal center B cells in draining lymph nodes, induced a durable and strong antibody response, especially the Th1-type IgG2a antibody response, and improved the cytotoxic T lymphocytes response. These results demonstrated that the CYP-Al NPs could generate robust humoral and cellular responses, and has the great potential to serve as an adjuvant delivery system.

Bivalent norovirus mRNA vaccine elicits cellular and humoral responses protecting human enteroids from GII.4 infection

Nucleoside-modified mRNA-LNP vaccines have revolutionized vaccine development against infectious pathogens due to their ability to elicit potent humoral and cellular immune responses. In this article, we present the results of the first norovirus vaccine candidate employing mRNA-LNP platform technology. The mRNA-LNP bivalent vaccine encoding the major capsid protein VP1 from GI.1 and GII.4 of human norovirus, generated high levels of neutralizing antibodies, robust cellular responses, and effectively protected human enteroids from infection by the most prevalent genotype (GII.4). These results serve as a proof of concept, demonstrating that a modified-nucleoside mRNA-LNP vaccine based on norovirus VP1 sequences can stimulate an immunogenic response in vivo and generates neutralizing antibodies capable of preventing viral infection in models of human gastrointestinal tract infection.

A spike-based mRNA vaccine that induces durable and broad protection against porcine deltacoronavirus in piglets.

As an emerging porcine enteropathogenic coronavirus, porcine deltacoronavirus (PDCoV) has the potential for cross-species transmission, attracting extensive attention. Messenger RNA (mRNA) vaccines are a promising option for combating emerging and re-emerging infectious diseases, as evidenced by the demonstrated efficacy of the COVID-19 mRNA vaccine. Here, we first demonstrated that PDCoV-S mRNA-lipid nanoparticle (LNP) vaccines could induce potent humoral and cellular immune responses in mice. An evaluation of passive immune protection of S mRNA vaccines in suckling piglets confirmed that the protective effect of mRNA vaccine was better than that of inactivated vaccine. This study suggests that the PDCoV-S mRNA-LNP vaccine may serve as a potential and novel vaccine candidate for combating PDCoV infection.

Lipo-pam™ adjuvanted herpes zoster vaccine induces potent gE-specific cellular and humoral immune responses

Herpes zoster (HZ), also known as shingles, is caused by the reactivation of latent varicella-zoster virus (VZV). Decreased VZV-specific T-cell immune responses significantly contribute to the development of HZ. Shingrix is a recombinant zoster vaccine that is currently used to prevent HZ. However, Shingrix has high reactogenicity and pain at the injection site due to QS21, one of the adjuvant components. In this study, we developed a new herpes zoster vaccine formulation called CVI-VZV-001, containing gE protein and a novel liposome-based adjuvant Lipo-pam™, which consists of two TLR agonists. We evaluated the immunogenicity of CVI-VZV-001 in mouse and rabbit models. CVI-VZV-001 elicited robust gE-specific T-cell immune responses and gE-specific antibody production. Specifically, CVI-VZV-001 induced polyfunctional CD4+ T cell populations that secrete multiple cytokines. Furthermore, CVI-VZV-001 sustained the gE-specific immune responses for up to six months after immunization. To ensure CVI-VZV-001’s safety for further development, we conducted a good laboratory practice (GLP) toxicity test, which confirmed that CVI-VZV-001 is safe for use. At present, CVI-VZV-001 is undergoing phase I clinical trials. This study suggests that CVI-VZV-001 can be a potent candidate for the HZ vaccine with high immunogenicity and safety.

A General Strategy toward Self-assembled Nanovaccine Based on Cationic Lentinan to Induce Potent Humoral and Cellular Immune Responses.

Adjuvants play a critical role in the induction of effective immune responses by vaccines. Here, a self-assembling nanovaccine platform that integrates adjuvant functions into the delivery vehicle is prepared. Cationic Lentinan (CLNT) is mixed with ovalbumin (OVA) to obtain a self-assembling nanovaccine (CLNTO nanovaccine), which induces the uptake and maturation of bone marrow dendritic cells (BMDCs) via the toll-like receptors 2/4 (TLR2/4)to produce effective antigen cross-presentation. CLNTO nanovaccines target lymph nodes (LNs) and induce a robust OVA-specific immune response via TLR and tumor necrosis factor (TNF) signaling pathways, retinoic acid-inducible gene I (RIG-I) receptor, and cytokine-cytokine receptor interactions. In addition, CLNTO nanovaccines are found that promote the activation of follicular helper T (Tfh) cells and induce the differentiation of germinal center (GC) B cells into memory B cells and plasma cells, thereby enhancing the immune response. Vaccination with CLNTO nanovaccine significantly inhibits the growth of ovalbumin (OVA)-expressing B16 melanoma cell (B16-OVA) tumors, indicating its great potential for cancer immunotherapy. Therefore, this study presents a simple, safe, and effective self-assembling nanovaccine that induces helper T cell 1 (Th1) and helper T cell (Th2) immune responses, making it an effective vaccine delivery system.

DNA programmed Mg-Al layered double hydroxide-based bi-adjuvant nanovaccines

Implementation of adjuvants is a requirement for inducing antigen-specific immune responses against infectious diseases. The conventional aluminum adjuvants used in clinical trials suffer from insufficient cellular immune response. Herein, we develop a bi-adjuvant nanovaccine containing receptor-binding domain (RBD) as antigen and DNA programmed Mg/Al layered double hydroxide (Mg/Al-LDH) as adjuvants, and thus achieve co-activation of potent humoral and cellular immune responses. The Mg/Al-LDH consisting of positively charged layers is firstly employed as scaffold to adsorb antigen via electrostatic interaction, and then CpG and dendritic cell (DC)-targeting aptamers co-encoded ultra-long DNA chains are easily decorated on the Mg/Al-LDH via interfacial assembly. The nanoscale formulations and interfacial targeting aptamers of nanovaccine facilitate their endocytosis by DC cells; the Mg/Al-LDH structure is acid-responsive and ensures the Al ions-inducing antigen cross-presentation for durable generation of antibody (Th2 immune response); and the agonist CpG in DNA chains can bind to the Toll-like receptor 9 (TLR 9) to activate cellular immunity (Th1 immune response). The bi-adjuvant nanovaccine fully combines the advantages of nanosheet alum-like adjuvant and precisely customization of DNA, and thus balances the Th1/Th2 immune response for compensating the deficiency of traditional alum adjuvant, providing a design guidance for creating next-generation of safe and efficient adjuvants in immunology.

Advances in Nucleic Acid Universal Influenza Vaccines.

Currently, vaccination with influenza vaccines is still an effective strategy to prevent infection by seasonal influenza virus in spite of some drawbacks with them. However, due to the rapid evolution of influenza viruses, including seasonal influenza viruses and emerging zoonotic influenza viruses, there is an urgent need to develop broad-spectrum influenza vaccines to cope with the evolution of influenza viruses. Nucleic acid vaccines might meet the requirements well. Nucleic acid vaccines are classified into DNA vaccines and RNA vaccines. Both types induced potent cellular and humoral immune responses, showing great promise for the development of universal influenza vaccines. In this review, the current status of an influenza universal nucleic acid vaccine was summarized.

Immunogenicity, safety and dual DIVA-like character of a recombinant candidate vaccine against neosporosis in cattle

Neosporosis is the major infectious cause of abortion and reproductive losses in cattle worldwide; however, there are no available vaccines or drugs to control this disease. Recently, a dual (positive and negative) DIVA-like (Differentiation of Infected from Vaccinated Animals) vaccine was evaluated in a pregnant mouse model of neosporosis, showing promising immunogenic and protective results. The current report aimed to study the safety, the dose-dependent immunogenicity and the dual DIVA-like character of a recombinant subunit vaccine composed of the major surface antigen from Neospora caninum (rNcSAG1) and the carrier/adjuvant Heat shock protein 81.2 from Arabidopsis thaliana (rAtHsp81.2) in cattle. Healthy heifers were separated and assigned to experimental groups A-F and subcutaneously immunized with 2 doses of vaccine formulations 30 days apart as follows: A (n = 4): 50 μg rNcSAG1 + 150 μg rAtHsp81.2; B (n = 4): 200 μg rNcSAG1 + 600 μg rAtHsp81.2; C (n = 4): 500 μg rNcSAG1 + 1,500 μg rAtHsp81.2; D (n = 3): 150 μg rAtHsp81.2; E (n = 3):1,500 μg rAtHsp81.2, and F (n = 3) 2 ml of sterile PBS. The immunization of heifers with the different vaccine or adjuvant doses (groups A-E) was demonstrated to be safe and did not modify the mean value of the evaluated serum biomarkers of metabolic function (GOT/ASP, GPT/ALT, UREA, Glucose and total proteins). The kinetics and magnitude of the immune responses were dose-dependent. The higher dose of the vaccine formulation (group C) stimulated a broad and potent humoral and cellular immune response, characterized by an IgG1/IgG2 isotype profile and IFN-γ secretion. In addition, this was the first time that dual DIVA-like character of a vaccine against neosporosis was demonstrated, allowing us to differentiate vaccinated from infected heifers by two different DIVA compliant test approaches. These results encourage us to evaluate its protective efficacy in infected pregnant cattle in the future.

The Key to Increase Immunogenicity of Next-Generation COVID-19 Vaccines Lies in the Inclusion of the SARS-CoV-2 Nucleocapsid Protein.

Vaccination is one of the most effective prophylactic public health interventions for the prevention of infectious diseases such as coronavirus disease (COVID-19). Considering the ongoing need for new COVID-19 vaccines, it is crucial to modify our approach and incorporate more conserved regions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to effectively address emerging viral variants. The nucleocapsid protein is a structural protein of SARS-CoV-2 that is involved in replication and immune responses. Furthermore, this protein offers significant advantages owing to the minimal accumulation of mutations over time and the inclusion of key T-cell epitopes critical for SARS-CoV-2 immunity. A novel strategy that may be suitable for the new generation of vaccines against COVID-19 is to use a combination of antigens, including the spike and nucleocapsid proteins, to elicit robust humoral and potent cellular immune responses, along with long-lasting immunity. The strategic use of multiple antigens aims to enhance vaccine efficacy and broaden protection against viruses, including their variants. The immune response against the nucleocapsid protein from other coronavirus is long-lasting, and it can persist up to 11 years post-infection. Thus, the incorporation of nucleocapsids (N) into vaccine design adds an important dimension to vaccination efforts and holds promise for bolstering the ability to combat COVID-19 effectively. In this review, we summarize the preclinical studies that evaluated the use of the nucleocapsid protein as antigen. This study discusses the use of nucleocapsid alone and its combination with spike protein or other proteins of SARS-CoV-2.

Engineering W/O/W pickering emulsion for the enhanced antigen delivery and immune responses

Tumor immunotherapy, particularly cancer vaccines, holds promise for combating cancer by harnessing tailored immune responses against malignant cells. However, conventional approaches face challenges in efficiently delivering antigens for optimal immune activation. Emulsion adjuvants, like MF59, enhance cellular uptake but struggle to induce robust CD8+ T cell responses. Here, we introduce a novel strategy employing a water-in-oil-in-water (W/O/W) multiple Pickering emulsion (mPE) for antigen delivery. The mPE, utilizing biocompatible, pH-sensitive particles, encapsulates antigens within the inner water phase, ensuring enhanced intracellular processing and dictating the intracellular fate of antigens for improved cross-presentation. In vitro and in vivo studies demonstrated that mPEs induced robust dendritic cells activation and antigen cross-presentation, leading to a significantly enhanced immune response. Notably, calcium phosphate-stabilized mPE (CaP-mPE) illustrated the more robust IFN-γ+ T cell responses. In comparison with traditional surfactant-stabilized multiple emulsions, CaP-mPE significantly inhibit tumor growth and effectively prolong the survival of tumor-bearing mice. This innovative approach offers a promising avenue for the development of effective cancer vaccines with potent cellular immune responses.

Plug-and-display nanoparticle immunization of the core epitope domain induces potent neutralizing antibody and cellular immune responses against PEDV

Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is widely spread worldwide and causes huge economic losses. The effective measure to control the viral infection is to develop ideal vaccines. Here, the monomeric core epitope domain (COE) of PEDV was displayed on the surface of nanoparticles (NPs) in order to develop a newer, safer and more effective subunit vaccine against PEDV. The monomeric COE was displayed on the mi3 protein, which self-assembles into nanoparticles composed of 60 subunits, using the SpyTag/SpyCatcher system. The size, Zeta potential, microstructure of the COE-mi3 virus-like particles (VLPs)were investigated. The COE-mi3 VLPs that possessed good security, stability and better retention can be more efficiently taken up by antigen-presenting cells (APCs) and help promote dendritic cells (DCs) maturation. Moreover, COE-mi3 VLPs could prominently improve specific antibody levels including neutralizing antibodies (NAbs), and serum IgG, mucosal IgA. Moreover, COE-mi3 VLPs elicited more activation of CD4+ and CD8+ T cells and production of IFN-γ and IL-4 cytokines. In particular, COE-mi3 VLPs is an effectual antigen-delivery platform to enhance germinal center (GC) B cell responses. This structure-based self-assembly of NP gives great potential to be developed as a new subunit vaccines attractive platform, and may also provide new ideas for the development of other enteric coronavirus vaccines.

A Quadrivalent mRNA Immunization Elicits Potent Immune Responses against Multiple Orthopoxviral Antigens and Neutralization of Monkeypox Virus in Rodent Models.

The global outbreak of the 2022 monkeypox virus infection of humans and the 2023 documentation of a more virulent monkeypox in the Democratic Republic of the Congo raised public health concerns about the threat of human-to-human transmission of zoonotic diseases. Currently available vaccines may not be sufficient to contain outbreaks of a more transmissible and pathogenic orthopoxvirus. Development of a safe, effective, and scalable vaccine against orthopoxviruses to stockpile for future emergencies is imminent. In this study, we have developed an mRNA vaccine candidate, ALAB-LNP, expressing four vaccinia viral antigens A27, L1, A33, and B5 in tandem in one molecule, and evaluated the vaccine immunogenicity in rodent models. Immunization of animals with the candidate mRNA vaccine induced a potent cellular immune response and long-lasting antigen-specific binding antibody and neutralizing antibody responses against vaccinia virus. Strikingly, the sera from the vaccine-immunized mice cross-reacted with all four homologous antigens of multiple orthopoxviruses and neutralized monkeypox virus in vitro, holding promise for this mRNA vaccine candidate to be used for protection of humans from the infection of monkeypox and other orthopoxvirus.

Self-Assembling Sulfated Lactobacillus Exopolysaccharide Nanoparticles as Adjuvants for SARS-CoV-2 Subunit Vaccine Elicit Potent Humoral and Cellular Immune Responses.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic since its onset in 2019, and the development of effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to induce potent and long-lasting immunity remains a priority. Herein, we prepared two Lactobacillus exopolysaccharide (EPS) nanoparticle adjuvants (NPs 7-4 and NPs 8-2) that were constructed by using sulfation-modified EPS and quaternization-modified chitosan. These two NPs displayed a spherical morphology with sizes of 39 and 47 nm. Furthermore, the zeta potentials of NPs 7-4 and NPs 8-2 were 50.40 and 44.40 mV, respectively. In vitro assays demonstrated that NPs could effectively adsorb antigenic proteins and exhibited a sustained release effect. Mouse immunization tests showed that the NPs induced the expression of cytokines and chemokines at the injection site and promoted the uptake of antigenic proteins by macrophages. Mechanically, the NPs upregulated the expression of pattern recognition receptors (toll-like receptors and nod-like receptors) and activated the immune response of T cells and the production of neutralizing antibodies. In addition, the NP adjuvants had favorable immune-enhancing effects in cats, which are of great significance for controlling the trans-host transmission and re-endemicity of SARS-CoV-2. Overall, we demonstrated that NP-adjuvanted SARS-CoV-2 receptor binding domain proteins could induce robust specific humoral and cellular immunity.

Ferritin-binding and ubiquitination-modified mRNA vaccines induce potent immune responses and protective efficacy against SARS-CoV-2

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) incessantly engenders mutating strains via immune escape mechanisms, substantially escalating the risk of severe acute respiratory syndrome. In this context, the urgent development of innovative and efficacious mRNA vaccines is imperative. In our study, we synthesized six unique mRNA vaccine formulations: the Receptor Binding Domain (RBD) monomer vaccine, RBD dimer (2RBD) vaccine, RBD-Ferritin (RBD-Fe) vaccine, ubiquitin-modified wild-type Nucleocapsid gene (WT-N) vaccine, rearranged Nucleocapsid gene (Re-N) vaccine, and an epitope-based (COVID-19 epitope) vaccine, all encapsulated within the lipid nanoparticle SM102. Immunization studies conducted on C57BL/6 mice with these vaccines revealed that the RBD monomer, RBD dimer (2RBD), and RBD-Fe vaccines elicited robust titers of specific antibodies, including neutralizing antibodies. In contrast, the wild-type N gene (WT-N), rearrange N gene (Re-N), and COVID-19 epitope vaccines predominantly induced potent cellular immune responses. Protective efficacy assays in golden hamsters demonstrated that vaccinated cohorts showed significant reduction in lung pathology, markedly lower viral loads in the lungs, nasal turbinates, and trachea, and substantially reduced transcriptional and expression levels of pro-inflammatory cytokines. Overall, our vaccine candidates pave the way for novel strategies in vaccine development against various infectious agents and establish a critical foundation for the formulation of advanced vaccines targeting emerging pathogens.

An inoculation site-retained mRNA vaccine induces robust immune responses against SARS-CoV-2 variants

mRNA-based vaccines and therapeutic agents hold great promise in prevention and treatment of human diseases, yet high percentage of systemic adverse effect in clinic remains a big safety concern. One major potential cause is a high level of leakage of the locally inoculated mRNA vaccine nanoparticles into circulation. We have screened and optimized a core-shell structured lipopolyplex (LPP) formulation for mRNA with a tissue-retention property. Upon intramuscular inoculation, the mRNA-encapsulated LPP nanoparticles were preferentially taken up by the phagocytic antigen-presentation cells, and potently promoted dendritic cell maturation. We applied the new formulation to prepare a prophylactic vaccine for SARS-CoV-2, and observed potent humoral and cellular immune responses from the vaccine in both murine models and non-human primates. More importantly, the vaccine demonstrated a benign safety profile in non-human primates, with limited side effects after repeated treatment with high dosages of LPP/mRNA. Taken together, the inoculation site-retained vaccine formulation serves as a promising vehicle for mRNA vaccines and therapeutic agents.

A dose escalation study to evaluate the safety of an aerosol BCG infection in previously BCG-vaccinated healthy human UK adults.

Tuberculosis (TB) is the leading cause of death worldwide from a single infectious agent. Bacillus Calmette-Guérin (BCG), the only licensed vaccine, provides limited protection. Controlled human infection models (CHIMs) are useful in accelerating vaccine development for pathogens with no correlates of protection; however, the need for prolonged treatment makes Mycobacterium tuberculosis an unethical challenge agent. Aerosolised BCG provides a potential safe surrogate of infection. A CHIM in BCG-vaccinated as well as BCG-naïve individuals would allow identification of novel BCG-booster vaccine candidates and facilitate CHIM studies in populations with high TB endemicity. The purpose of this study was to evaluate the safety and utility of an aerosol BCG CHIM in historically BCG-vaccinated volunteers. There were 12 healthy, historically BCG-vaccinated UK adults sequentially enrolled into dose-escalating groups. The first three received 1 × 104 CFU aerosol BCG Danish 1331 via a nebuliser. After safety review, subsequent groups received doses of 1 × 105 CFU, 1 × 106 CFU, or 1 × 107 CFU. Safety was monitored through self-reported adverse events (AEs), laboratory tests, and lung function testing. Immunology blood samples were taken pre-infection and at multiple timepoints post-infection. A bronchoalveolar lavage (BAL) taken 14 days post-infection was analysed for presence of live BCG. No serious AEs occurred during the study. Solicited systemic and respiratory AEs were frequent in all groups, but generally short-lived and mild in severity. There was a trend for more reported AEs in the highest-dose group. No live BCG was detected in BAL from any volunteers. Aerosol BCG induced potent systemic cellular immune responses in the highest-dose group 7 days post-infection. Aerosol BCG infection up to a dose of 1 × 107 CFU was well-tolerated in historically BCG-vaccinated healthy, UK adults. No live BCG was detected in the BAL fluid 14 days post-infection despite potent systemic responses, suggesting early clearance. Further work is needed to expand the number of volunteers receiving BCG via the aerosol route to refine and establish utility of this aerosol BCG CHIM. https://clinicaltrials.gov/, identifier NCT04777721.

A novel mucosal bivalent vaccine of EV-A71/EV-D68 adjuvanted with polysaccharides from Ganoderma lucidum protects mice against EV-A71 and EV-D68 lethal challenge

BackgroundHuman enteroviruses A71 (EV-A71) and D68 (EV-D68) are the suspected causative agents of hand-foot-and-mouth disease, aseptic meningitis, encephalitis, acute flaccid myelitis, and acute flaccid paralysis in children. Until now, no cure nor mucosal vaccine existed for EV-A71 and EV-D68. Novel mucosal bivalent vaccines are highly important for preventing EV-A71 and EV-D68 infections.MethodsIn this study, formalin-inactivated EV-A71 and EV-D68 were used as antigens, while PS-G, a polysaccharide from Ganoderma lucidum, was used as an adjuvant. Natural polysaccharides have the characteristics of intrinsic immunomodulation, biocompatibility, low toxicity, and safety. Mice were immunized intranasally with PBS, EV-A71, EV-D68, or EV-A71 + EV-D68, with or without PS-G as an adjuvant.ResultsThe EV-A71 + EV-D68 bivalent vaccine generated considerable EV-A71- and EV-D68-specific IgG and IgA titres in the sera, nasal washes, saliva, bronchoalveolar lavage fluid, and feces. These antibodies neutralized EV-D68 and EV-A71 infectivity. They also cross-neutralized infections by different EV-D68 and EV-A71 sub-genotypes. Furthermore, compared with the PBS group, EV-A71 + EV-D68 + PS-G-vaccinated mice exhibited an increased number of EV-D68- and EV-A71-specific IgA- and IgG-producing cells. In addition, T-cell proliferative responses, and IFN-γ and IL-17 secretion in the spleen were substantially induced when PS-G was used as an adjuvant with EV-A71 + EV-D68. Finally, in vivo challenge experiments demonstrated that the immune sera induced by EV-A71 + EV-D68 + PS-G conferred protection in neonate mice against lethal EV-A71 and EV-D68 challenges as indicated by the increased survival rate and decreased clinical score and viral RNA tissue expression. Taken together, all EV-A71/EV-D68 + PS-G-immunized mice developed potent specific humoral, mucosal, and cellular immune responses to EV-D68 and EV-A71 and were protected against them.ConclusionsThese findings demonstrated that PS-G can be used as a potential adjuvant for EV-A71 and EV-D68 bivalent mucosal vaccines. Our results provide useful information for the further preclinical and clinical development of a mucosal bivalent enterovirus vaccine against both EV-A71 and EV-D68 infections.Graphical

Durable natural killer cell response after three doses of SARS-CoV-2 inactivated vaccine in HIV-infected individuals.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection. However, it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer (NK) cell response in people living with human immunodeficiency virus (PLWH) and healthy individuals. Forty-seven PLWH and thirty healthy controls (HCs) inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study. The effect of SARS-CoV-2 vaccine on NK cell frequency, phenotype, and function in PLWH and HCs was evaluated by flow cytometry, and the response of NK cells to SARS-CoV-2 Omicron Spike (SARS-2-OS) protein stimulation was also evaluated. SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH, which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine. However, in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers. Additionally, the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0, 4 and 12weeks, but the percentage of CD16 + NK cells in PLWH was significantly higher than that in HCs at 2, 4 and 12weeks after the third dose of vaccine. Interestingly, the frequency of CD16 + NK cells was significantly negatively correlated with the proportion of CD107a + NK cells in PLWH at each time point after the third dose. Similarly, this phenomenon was also observed in HCs at 0, 2, and 4 weeks after the third dose. Finally, regardless of whether NK cells were stimulated with SARS-2-OS or not, we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs. s:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells, indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.

Single-injection subunit vaccine for rabies prevention using lentinan as adjuvant

Current rabies vaccines require 5 doses to provide full protection from the deadly virus, which significantly reduce the compliance of recipients. To minimize the number of immunizations herein single injection vaccines were developed. First a single injection vaccine was designed using rabies virus glycoprotein (G protein) as antigen. A time-controlled release system which uses dynamic layer-by-layer films as erodible coating was employed to accomplish multiply pulsatile releases of G protein. The single-injection vaccine elicits potent humoral and cellular immune responses comparable to the corresponding multi-dose ordinary vaccines because of their similar release pattern of G protein. To further improve its performance, a second single injection vaccine, in which lentinan was added as adjuvant, was designed. This single-injection vaccine again elicits humoral and cellular immune responses comparable to the corresponding multi-dose ordinary vaccines because of their similar release pattern of antigen and adjuvant. In addition, the second single-injection vaccine elicits higher level immune response and provides higher efficiency on virus inhibition than the first one because lentinan can booster immune response.

Bestatin, A Pluripotent Immunomodulatory Small Molecule, Drives Robust and Long-Lasting Immune Responses as an Adjuvant in Viral Vaccines.

An inactivated whole-virus vaccine is currently used to prevent foot-and-mouth disease (FMD). Although this vaccine is effective, it offers short-term immunity that requires regular booster immunizations and has several side effects, including local reactions at the vaccination site. To address these limitations, herein, we evaluated the efficacy of bestatin as a novel small molecule adjuvant for inactivated FMD vaccines. Our findings showed that the FMD vaccine formulated with bestatin enhanced early, intermediate-, and particularly long-term immunity in experimental animals (mice) and target animals (pigs). Furthermore, cytokines (interferon (IFN)α, IFNβ, IFNγ, and interleukin (IL)-29), retinoic acid-inducible gene (RIG)-I, and T-cell and B-cell core receptors (cluster of differentiation (CD)28, CD19, CD21, and CD81) markedly increased in the group that received the FMD vaccine adjuvanted with bestatin in pigs compared with the control. These results indicate the significant potential of bestatin to improve the efficacy of inactivated FMD vaccines in terms of immunomodulatory function for the simultaneous induction of potent cellular and humoral immune response and a long-lasting memory response.