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SARS-CoV-2, the causal agent of the COVID-19 pandemic, is characterized by rapid evolution, which poses a significant public health challenge. Effective vaccines that provide robust protection, elicit strong immune responses, exhibit favorable safety profiles, and enable cost-effective large-scale production are crucial. The RBD-Fc-based Betuvax-CoV-2 vaccine has previously demonstrated a favorable safety profile and induced a significant anti-SARS-CoV-2 humoral immune response in clinical trials. Due to the rapid evolution and emergence of new SARS-CoV-2 strains, the relevance of bivalent vaccine formulations has increased. Methods: This study compared the neutralizing capacity of monovalent and bivalent vaccine formulations against different SARS-CoV-2 strains detected with a SARS-CoV-2 microneutralization assay (MNT). Findings: The monovalent Wuhan-based vaccine generated neutralizing antibodies against the Wuhan and Omicron BA.2 variants but not the distinct Omicron BQ.1 strain. Conversely, the monovalent BA.2-based vaccine induced neutralizing antibodies against both Omicron strains but not Wuhan. While the bivalent Wuhan and BA.2-based vaccine was effective against strains containing the same antigens, it was insufficient to neutralize the distinctive BQ.1 strain at a small dosage. Interpretation: These findings suggest that the vaccine composition should closely match the circulating SARS-CoV-2 strain to elicit the optimal neutralizing antibody response and include the appropriate dosage. Moreover, this study did not find additional advantages of using the bivalent form over the monovalent form for the vaccination against a single prevailing SARS-CoV-2 strain. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic continues to cause infections and deaths, which are attributable to the SARS-CoV-2 Omicron variant of concern (VOC). Moderna's response to the declining protective efficacies of current SARS-CoV-2 vaccines against Omicron was to develop a bivalent booster vaccine based on the Spike (S) protein from the Wuhan and Omicron BA.4/BA.5 strains. This approach, while commendable, is unfeasible in light of rapidly emerging mutated viral strains. PubMed and Google Scholar were systematically reviewed for peer-reviewed papers up to January 2024. Articles included focused on specific themes such as the clinical history of recombinant protein vaccine development against different diseases, including COVID-19, the production of recombinant protein vaccines using different host expression systems, aspects to consider in recombinant protein vaccine development, and overcoming problems associated with large-scale recombinant protein vaccine production. In silico approaches to identify conserved and immunogenic epitopes could provide broad protection against SARS-CoV-2 VOCs but require validation in animal models. The recombinant protein vaccine development platform has shown a successful history in clinical development. Recombinant protein vaccines incorporating conserved epitopes may utilize a number of expression systems, such as yeast (Saccharomyces cerevisiae), baculovirus-insect cells (Sf9 cells), and Escherichia coli (E. coli). Current multi-epitope subunit vaccines against SARS-CoV-2 utilizing synthetic peptides are unfeasible for large-scale immunizations. Recombinant protein vaccines based on conserved and immunogenic proteins produced using E. coli offer high production yields, convenient purification, and cost-effective production of large-scale vaccine quantities capable of protecting against the SARS-CoV-2 D614G strain and its VOCs. [ABSTRACT FROM AUTHOR]

Background: Infection with Helicobacter pylori (Hp) mostly occurs during childhood, and persistent infection may lead to severe gastric diseases and even gastric cancer. Currently, the primary method for eradicating Hp is through antibiotic treatment. However, the increasing multidrug resistance in Hp strains has diminished the effectiveness of antibiotic treatments. Vaccination could potentially serve as an effective intervention to resolve this issue. Aims: Through extensive research and analysis of the vital protein characteristics involved in Hp infection, we aim to provide references for subsequent vaccine antigen selection. Additionally, we summarize the current research and development of Hp vaccines in order to provide assistance for future research. Materials and Methods: Utilizing the databases PubMed and the Web of Science, a comprehensive search was conducted to compile articles pertaining to Hp antigens and vaccines. The salient aspects of these articles were then summarized to provide a detailed overview of the current research landscape in this field. Results: Several potential antigens have been identified and introduced through a thorough understanding of the infection process and pathogenic mechanisms of Hp. The conserved and widely distributed candidate antigens in Hp, such as UreB, HpaA, GGT, and NAP, are discussed. Proteins such as CagA and VacA, which have significant virulence effects but relatively poor conservatism, require further evaluation. Emerging antigens like HtrA and dupA have significant research value. In addition, vaccines based on these candidate antigens have been compiled and summarized. Conclusions: Vaccines are a promising method for preventing and treating Hp. While some Hp vaccines have achieved promising results, mature products are not yet available on the market. Great efforts have been directed toward developing various types of vaccines, underscoring the need for developers to select appropriate antigens and vaccine formulations to improve success rates. [ABSTRACT FROM AUTHOR]

Chlamydia (C.) trachomatis, a leading cause of sexually transmitted infections (STIs) worldwide, continues to be a significant public health concern. The majority of infections are asymptomatic and, when left untreated, severe sequelae such as infertility and chronic pelvic pain can occur. Despite decades of research, an effective vaccine remains elusive. This review focuses on the potential of Major Outer Membrane Protein (MOMP)-derived constructs as promising candidates for C. trachomatis vaccination. MOMP, the most abundant protein in the outer membrane of C. trachomatis, has been a focal point of vaccine research over the years due to its antigenic properties. To overcome issues associated with the use of full MOMP as a vaccine antigen, derivative constructs have been studied. As these constructs are often not sufficiently immunogenic, antigen delivery systems or accompanying adjuvants are required. Additionally, several immunization routes have been explored with these MOMP-derived vaccine antigens, and determining the optimal route remains an ongoing area of research. Future directions and challenges in the field of C. trachomatis vaccination are discussed. [ABSTRACT FROM AUTHOR]

Bacterium-like particles (BLPs) have gained significant attention in vaccine development due to their potential as effective immune enhancers and antigen delivery systems. BLPs are generated by boiling lactic acid bacteria in an acidic solution and are devoid of proteins and nucleic acids, offering advantages in terms of ease of preparation, high safety, and good stability. Furthermore, by employing protein anchor (PA), heterogeneous antigens can be efficiently displayed on the surface of BLPs, resulting in enhanced delivery effectiveness. Despite these benefits, most BLP-based vaccines are currently administered via injection or intranasal delivery, with oral delivery remaining limited. This limitation is primarily due to the harsh environment of the gastrointestinal tract, which degrades the antigens displayed on the surface of these particles. To enhance the efficacy of oral immunization with subunit vaccines, we developed a simple and rapid method for self-assembling a lipid membrane onto the surface of BLPs vaccines, achieving an encapsulation efficiency of up to 99%, and the combination has good biosafety. The novel oral delivery system not only preserves the adjuvant activity of BLPs but also efficiently protects antigens from adverse gastrointestinal environments, increasing the absorption of the vaccine in intestinal Peyer’s patches (PPs). Oral immunization was required only once, and protection after the challenge was up to 100%. Furthermore, we observed rapid immunity and cross-protection. Transcriptome analysis of the small intestine suggested that immune enhancement probably be exerted by promoting the absorption and transport of antigens. Therefore, we posit that the design of this new oral delivery system presents a novel approach to advancing the development of oral subunit vaccines.

Vaccines represent one of the most powerful and cost-effective innovations for controlling a wide range of infectious diseases caused by various viruses and bacteria. Unlike mRNA and DNA-based vaccines, subunit vaccines carry no risk of insertional mutagenesis and can be lyophilized for convenient transportation and long-term storage. However, existing adjuvants are often associated with toxic effect and reactogenicity, necessitating expanding the repertoire of adjuvants with better biocompatibility, for instance, designing self-adjuvating polymeric carriers. We herein report a novel subunit vaccine delivery platform constructed via in situ free radical polymerization of C7A (2-(Hexamethyleneimino) ethyl methacrylate) and acrylamide around the surface of individual protein antigens. Using ovalbumin (OVA) as a model antigen, we observed substantial increases in both diameter (∼70 nm) and surface potential (−1.18 mV) following encapsulation, referred to as n(OVA)C7A. C7A's ultra pH sensitivity with a transition pH around 6.9 allows for rapid protonation in acidic environments. This property facilitates crucial processes such as endosomal escape and major histocompatibility complex (MHC)-I-mediated antigen presentation, culminating in the substantial CD8+ T cell activation. Additionally, compared to OVA nanocapsules without the C7A components and native OVA without modifications, we observed heightened B cell activation within the germinal center, along with remarkable increases in serum antibody and cytokine production. It's important to note that mounting evidence suggests that adjuvant effects, particularly its targeted stimulation of type I interferons (IFNs), can contribute to advantageous adaptive immune responses. Beyond its exceptional potency, the nanovaccine also demonstrated robust formation of immune memory and exhibited a favorable biosafety profile. These findings collectively underscore the promising potential of our nanovaccine in the realm of immunotherapy and vaccine development. Schematic illustration of the preparation process of bioresponsive nanovaccine (n(OVA)C7A) and the induction of adaptive immune responses. Firstly, pH-responsive 2-(hexamethyleneimino) ethyl methacrylate (C7A-MA) and acrylamide (AAm), along with the biodegradable crosslinker N,N′ -Bis(acryloyl) cystamine, were initially enriched on the surface of OVA through non-covalent bonding. Secondly, after subcutaneous injection of mice at the hind footpad, the developed nanovaccine n(OVA)C7A rapidly were accumulated in lymph nodes and promoted the uptake and maturation of lymph node-resident DCs, triggering a series of adaptive humoral and cellular immune responses. [Display omitted] • Vaccine carriers with dispersed C7A groups form polymer networks encompassing the antigen. • C7A's ultra pH sensitivity facilitates endosomal escape and MHC-I-mediated antigen presentation. • Self-adjuvanting polymeric nanovaccines (n(OVA)C7A) foster substantial cytotoxic T cell activation and IFNs production. • This nanoplatform has the potential to deliver a variety of protein antigens against viral infections and cancer. [ABSTRACT FROM AUTHOR]

Chinese Hamster Ovary (CHO) cells, employed primarily for manufacturing monoclonal antibodies and other recombinant protein (r-protein) therapeutics, are emerging as a promising host for vaccine antigen production. This is exemplified by the recently approved CHO cell-derived subunit vaccines (SUV) against respiratory syncytial virus (RSV) and varicella-zoster virus (VZV), as well as the enveloped virus-like particle (eVLP) vaccine against hepatitis B virus (HBV). Here, we summarize the design, production, and immunogenicity features of these vaccine and review the most recent progress of other CHO-derived vaccines in pre-clinical and clinical development. We also discuss the challenges associated with vaccine production in CHO cells, with a focus on ensuring viral clearance for eVLP products. [ABSTRACT FROM AUTHOR]

Subunit vaccines are an important platform for controlling current and emerging infectious diseases. The lymph nodes are the primary site generating the humoral response and delivery of antigens to these sites is critical to effective immunization. Indeed, the duration of antigen exposure within the lymph node is correlated with the antibody response. While current licensed vaccines are typically given through the intramuscular route, injecting vaccines subcutaneously allows for direct access to lymphatic vessels and therefore can enhance the transfer of antigen to the lymph nodes. However, protein subunit antigen uptake into the lymph nodes is inefficient, and subunit vaccines require adjuvants to stimulate the initial immune response. Therefore, formulation strategies have been developed to enhance the exposure of subunit proteins and adjuvants to the lymph nodes by increasing lymphatic uptake or prolonging the retention at the injection site. Given that lymph node exposure is a crucial consideration in vaccine design, in depth analyses of the pharmacokinetics of antigens and adjuvants should be the focus of future preclinical and clinical studies. This review will provide an overview of formulation strategies for targeting the lymphatics and prolonging antigen exposure and will discuss pharmacokinetic evaluations which can be applied toward vaccine development. [ABSTRACT FROM AUTHOR]

The unprecedented global impact caused by SARS-CoV-2 imposed huge health and economic challenges, highlighting the urgent need for safe and effective vaccines. The receptor-binding domain (RBD) of SARS-CoV-2 is the major target for neutralizing antibodies and for vaccine formulations. Nonetheless, the low immunogenicity of the RBD requires the use of alternative strategies to enhance its immunological properties. Here, we evaluated the use of a subunit vaccine antigen generated after the genetic fusing of the RBD with a mouse IgG antibody. Subcutaneous administration of RBD-IgG led to the extended presence of the protein in the blood of immunized animals and enhanced RBD-specific IgG titers. Furthermore, RBD-IgG immunized mice elicited increased virus neutralizing antibody titers, measured both with pseudoviruses and with live original (Wuhan) SARS-CoV-2. Immunized K18-hACE2 mice were fully resistant to the lethal challenge of the Wuhan SARS-CoV-2, demonstrated by the control of body-weight loss and virus loads in their lungs and brains. Thus, we conclude that the genetic fusion of the RBD with an IgG molecule enhanced the immunogenicity of the antigen and the generation of virus-neutralizing antibodies, supporting the use of IgG chimeric antigens as an approach to improve the performance of SARS-CoV-2 subunit vaccines. [ABSTRACT FROM AUTHOR]

Infection with influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) poses a significant risk to human life, health, and the global economy. Vaccination is one of the most effective strategies in the fight against infectious viruses. In this study, we, for the first time, have evaluated the immunogenicity and protective effect of an influenza/SARS‐CoV‐2 Omicron subunit combined vaccine adjuvanted with MF59 and administered to BALB/c mice. Results showed that the combined vaccine induced high levels of IgG, IgG1, and IgG2a antibodies, as well as influenza A H1N1/California/2009 virus‐specific hemagglutination‐inhibiting antibodies in BALB/c mice. Moreover, this subunit combined vaccine induced high titers of neutralization antibodies against SARS‐CoV‐2 Omicron sublineage BA.5 pseudovirus and effectively reduced the viral load of authentic SARS‐CoV‐2 Omicron sublineage BA.5.2 in the cell culture supernatants. These results suggested that this subunit combined vaccine achieved protective effect against both H1N1 A/California/07/2009 strain and SARS‐CoV‐2 Omicron BA.5.2 variant. It is therefore expected that this study will establish the scientific foundation for the next‐step development of combined vaccines against other strains or variants of IAV and SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, the causal agent of the COVID-19 pandemic, is characterized by rapid evolution, which poses a significant public health challenge. Effective vaccines that provide robust protection, elicit strong immune responses, exhibit favorable safety profiles, and enable cost-effective large-scale production are crucial. The RBD-Fc-based Betuvax-CoV-2 vaccine has previously demonstrated a favorable safety profile and induced a significant anti-SARS-CoV-2 humoral immune response in clinical trials. Due to the rapid evolution and emergence of new SARS-CoV-2 strains, the relevance of bivalent vaccine formulations has increased. Methods: This study compared the neutralizing capacity of monovalent and bivalent vaccine formulations against different SARS-CoV-2 strains detected with a SARS-CoV-2 microneutralization assay (MNT). Findings: The monovalent Wuhan-based vaccine generated neutralizing antibodies against the Wuhan and Omicron BA.2 variants but not the distinct Omicron BQ.1 strain. Conversely, the monovalent BA.2-based vaccine induced neutralizing antibodies against both Omicron strains but not Wuhan. While the bivalent Wuhan and BA.2-based vaccine was effective against strains containing the same antigens, it was insufficient to neutralize the distinctive BQ.1 strain at a small dosage. Interpretation: These findings suggest that the vaccine composition should closely match the circulating SARS-CoV-2 strain to elicit the optimal neutralizing antibody response and include the appropriate dosage. Moreover, this study did not find additional advantages of using the bivalent form over the monovalent form for the vaccination against a single prevailing SARS-CoV-2 strain.

• Trimeric S, S1, COEs, and two adjuvants were selected to evaluate immune effects. • S/M103 elicited neutralizing antibodies, T cells, B cells, and NK cells in mice. • S/M103 induced high levels of neutralizing antibodies, IFN-γ, and IL-4 in piglets. • S/M103 provided protection against viral challenge in piglets. Porcine epidemic diarrhea virus (PEDV) has caused serious economic losses to the pig husbandry worldwide, and the effects of existing commercialized vaccines are suboptimal. Therefore, research to develop an efficacious vaccine for prevention and control of PEDV is essential. In this study, we designed and produced trimerized proteins of full-length PEDV spike (S) protein, S1 subunit, and a tandem of multiple epitopes of S protein using an efficient mammalian expression vector system in HEK 293F cells. The immunogenicity of two commercial adjuvants, M401 and M103, was also evaluated in mice. Enzyme-linked immunosorbent assays demonstrated that all immunized mice generated highly systemic PEDV S-specific IgG and IgA antibodies. Mice in S/M103-immunized group generated the highest neutralizing antibody titer with 1:96. Compared with control group, the subunit vaccines elicited multifunctional CD3+CD4+ and CD3+CD8+ T cells, B220+CD19+ B cells, and CD3-CD49b+ natural killer cells in the spleen. PEDV S/M103 vaccine, which had the best immune effect, was selected for further evaluation in piglets. Immunization with S/M103 vaccine induced high levels of S-specific IgG, IgA, and neutralizing antibodies, and increased the proliferation of peripheral blood mononuclear cells and the expression levels of interferon-γ and interleukin-4 in peripheral blood of piglets. Virus challenge test results showed significantly lower diarrheal index scores and fecal viral loads, and less pathological damage to the intestines in S/M103-immunized piglets than in controls, indicating that S/M103 provides good protection against the virulent virus challenge. Our findings suggest that trimeric PEDV S/M103 has potential as a clinical vaccine candidate. [ABSTRACT FROM AUTHOR]

The emergence of COVID-19 has posed an unprecedented global health crisis, challenging the healthcare systems worldwide. Amidst the rapid development of several vaccine formulations, protein subunit vaccines have emerged as a promising approach. This article provides an in-depth evaluation of the role of protein subunit vaccines in the management of COVID-19. Leveraging viral protein fragments, particularly the spike protein from SARS-CoV-2, these vaccines elicit a targeted immune response without the risk of inducing disease. Notably, the robust safety profile of protein subunit vaccines makes them a compelling candidate in the management of COVID-19. Various innovative approaches, including reverse vaccinology, virus like particles, and recombinant modifications are incorporated to develop protein subunit vaccines. In addition, the utilization of advanced manufacturing techniques facilitates large-scale production, ensuring widespread distribution. Despite these advancements, challenges persist, such as the requirement for cold-chain storage and the necessity for booster doses. This article evaluates the formulation and applications of protein subunit vaccines, providing a comprehensive overview of their clinical development and approvals in the context of COVID-19. By addressing the current status and challenges, this review aims to contribute to the ongoing discourse on optimizing protein subunit vaccines for effective pandemic control. [Display omitted] [ABSTRACT FROM AUTHOR]

Vibriosis is caused by Vibrio anguillarum in various species of aquaculture. A novel, secure, and stable vaccine is needed to eradicate vibriosis. Here, for reverse vaccinology and plant-based expression, the outer membrane protein K (OmpK) of V. anguillarum was chosen due to its conserved nature in all Vibrio species. OmpK, an ideal vaccine candidate against vibriosis, demonstrated immunogenic, non-allergic, and non-toxic behavior by using various bioinformatics tools. Docking showed the interaction of the OmpK model with TLR-5. In comparison to costly platforms, plants can be used as alternative and economic bio-factories to produce vaccine antigens. We expressed OmpK antigen in Nicotiana tabacum using Agrobacterium -mediated transformation. The expression vector was constructed using Gateway® cloning. Transgene integration was verified by polymerase chain reaction (PCR), and the copy number via qRT-PCR, which showed two copies of transgenes. Western blotting detected monomeric form of OmpK protein. The total soluble protein (TSP) fraction of OmpK was equivalent to 0.38% as detected by ELISA. Mice and fish were immunized with plant-derived OmpK antigen, which showed a significantly high level of anti-OmpK antibodies. The present study is the first report of OmpK antigen expression in higher plants for the potential use as vaccine in aquaculture against vibriosis, which could provide protection against multiple Vibrio species due to the conserved nature OmpK antigen. • Outer membrane protein K (OmpK) demonstrates immunogenic potential in silico. • OmpK antigen for immunization is produced in cost-effective plant bio-factories. • OmpK produced in plants induced a strong antibody response in mice and fish. • Vibriosis in aquaculture may be eradicated by cost-effective subunit vaccination. [ABSTRACT FROM AUTHOR]

Subunit vaccines based on antigen proteins or epitopes of pathogens or tumors show advantages in immunological precision and high safety, but are often limited by their low immunogenicity. Adjuvants can boost immune responses by stimulating immune cells or promoting antigen uptake by antigen presenting cells (APCs), yet existing clinical adjuvants struggle in simultaneously achieving these dual functions. Additionally, the spatial organization of antigens might be crucial to their immunogenicity. Hence, superior adjuvants should potently stimulate the immune system, precisely arrange antigens, and effectively deliver antigens to APCs. Recently, precisely organizing and delivering antigens with the unique editability of DNA nanostructures has been proposed, presenting unique abilities in significantly improving the immunogenicity of antigens. In this minireview, we will discuss the principles behind using DNA nanostructures as self‐adjuvant carriers and review the latest advancements in this field. The potential and challenges associated with self‐adjuvant DNA nanostructures will also be discussed. [ABSTRACT FROM AUTHOR]

(1) Background: Avian influenza has attracted widespread attention because of its severe effect on the poultry industry and potential threat to human health. The H9N2 subtype of avian influenza viruses was the most prevalent in chickens, and there are several commercial vaccines available for the prevention of the H9N2 subtype of avian influenza viruses. However, due to the prompt antigenic drift and antigenic shift of influenza viruses, outbreaks of H9N2 viruses still continuously occur, so surveillance and vaccine updates for H9N2 subtype avian influenza viruses are particularly important. (2) Methods: In this study, we constructed a stable Chinese hamster ovary cell line (CHO) to express the H9 hemagglutinin (HA) protein of the major prevalent H9N2 strain A/chicken/Daye/DY0602/2017 with genetic engineering technology, and then a subunit H9 avian influenza vaccine was prepared using the purified HA protein with a water-in-oil adjuvant. (3) Results: The results showed that the HI antibodies significantly increased after vaccination with the H9 subunit vaccine in specific-pathogen-free (SPF) chickens with a dose–dependent potency of the immunized HA protein, and the 50 μg or more per dose HA protein could provide complete protection against the H9N2 virus challenge. (4) Conclusions: These results indicate that the CHO expression system could be a platform used to develop the subunit vaccine against H9 influenza viruses in chickens. [ABSTRACT FROM AUTHOR]

Neospora caninum is an apicomplexan protozoan that causes neosporosis, which has a high economic impact on cattle herds with no available vaccine. During infection, the secretion of dense granules and the expression of surface antigens play an important role in hosting immunomodulation. However, some epitopes of those antigens are immunogenic, and using these fractions could improve the subunit antigens in vaccine design. This study evaluates the recombinant peptides rsNcGRA1 and rsNcSAG4 derived from NcGRA1 and NcSAG4 native antigens as vaccine candidates produced by a fermentative process in the yeast culture system of Komagataella phaffii strain Km71, confirmed by colony PCR, SDS-PAGE, and western blotting. The assay was conducted in BALB/c mice using the peptides at low (25 μg) and standard (50 μg) dosages in monovalent and combined administrations at three time points with saponin as an adjuvant assessing the immunogenicity by antibodies response and cytokine production. We challenge the females after pregnancy confirmation using 2 × 105 NC-1 tachyzoites previously propagated in Vero cells. We assessed the chronic infection in dams and vertical transmission in the offspring by PCR and histopathology. Mice, especially those immunised with combined peptides and monovalent rsNcGRA1 at a standard dose, controlling the chronic infection in dams with the absence of clinical manifestations, showed an immune response with induction of IgG1, a proper balance between Th1/Th2 cytokines and reduced vertical transmission in the pups. In contrast, dams inoculated with a placebo vaccine showed clinical signs, low-scored brain lesions, augmented chronic infection with 80% positivity, 31% mortality in pups, and 81% vertical transmission. These findings indicate that rsNcGRA1 peptides in monovalent and combined with rsNCSAG4 at standard dose are potential vaccine candidates and improve the protective immune response against neosporosis in mice. [ABSTRACT FROM AUTHOR]

Chlamydia (C.) trachomatis, a leading cause of sexually transmitted infections (STIs) worldwide, continues to be a significant public health concern. The majority of infections are asymptomatic and, when left untreated, severe sequelae such as infertility and chronic pelvic pain can occur. Despite decades of research, an effective vaccine remains elusive. This review focuses on the potential of Major Outer Membrane Protein (MOMP)-derived constructs as promising candidates for C. trachomatis vaccination. MOMP, the most abundant protein in the outer membrane of C. trachomatis, has been a focal point of vaccine research over the years due to its antigenic properties. To overcome issues associated with the use of full MOMP as a vaccine antigen, derivative constructs have been studied. As these constructs are often not sufficiently immunogenic, antigen delivery systems or accompanying adjuvants are required. Additionally, several immunization routes have been explored with these MOMP-derived vaccine antigens, and determining the optimal route remains an ongoing area of research. Future directions and challenges in the field of C. trachomatis vaccination are discussed.

Vaccination using live attenuated vaccines (LAVs) is considered the most effective method for control of lumpy skin disease (LSD). However, this method is limited by safety concerns, with reports of adverse reactions following vaccination. This study evaluates A27L and L1R which are essential proteins for virus attachment and membrane fusion as recombinant sub-unit vaccines against LSD. These proteins were recombinantly expressed in Escherichia coli and purified using affinity chromatography. Purified proteins were formulated individually (A27L or L1R) and in combination (A27L and L1R) with 10% (w/w) Montanide™ Gel 01 PR adjuvant at a final antigen dose of 20 µg per protein. The safety and immunogenicity of these formulations were evaluated in rabbits in a 42-day clinical trial. Animals were vaccinated on day 0 and boost injection administered 21 days later. No reduced morbidity, increased temperature and any other clinical signs were recorded in vaccinated animals for all three vaccine formulations. The highest neutralizing antibody response was detected on day 42 post-primary vaccination for all formulations when using serum neutralising assay. The neutralisation data correlates with antibody titres quantified using a whole cell ELISA. Evaluating the combination of A27L and L1R as potential diagnostic reagents showed highest sensitivity for detection of antibodies against LSD when compared to individual proteins. This study reports the immunogenicity of recombinant A27L and L1R combination for successful application in LSD vaccine development. Furthermore, these proteins demonstrated the potential use in LSD diagnostics.

• Effective vaccines could reduce the rates of systemic Salmonella infection. • CD4 TRM are required for complete protection against iNTS in mice. • Previous vaccine failure could be due to an inability to induce CD4 TRM. Salmonella infections cause a wide range of intestinal and systemic disease that affects global human health. While some vaccines are available, they do not mitigate the impact of Salmonella on endemic areas. Research using Salmonella mouse models has revealed the important role of CD4 T cells and antibody in the development of protective immunity against Salmonella infection. Recent work points to a critical role for hepatic tissue-resident memory lymphocytes in naturally acquired immunity to systemic infection. Thus, understanding the genesis and function of this Salmonella -specific population is an important objective and is the primary focus of this review. Greater understanding of how these memory lymphocytes contribute to bacterial elimination could suggest new approaches to vaccination against an important human pathogen. [ABSTRACT FROM AUTHOR]

Immunostimulants and vaccines are the main means for controlling infectious diseases and searching highly effective and low toxic immunestimulants has always been the focus of researchers. The MetchnikowinII (MetII) had been expressed by us and exhibited both antibacterial and antifungal activities, in this study, we evaluated its potential for an adjuvant effect. In chickens, antigen-specific immunoglobulin Gs (IgGs) were increased after MetII adjuvanted vaccination using the Ptfa protein. Compared to group Ptfa + iFA, which was only adjuvanted with incomplete Freund's adjuvant (iFA), the antibody titers of the group Ptfa + iFA + Met20 µg·mL-1 (PFM20) and Ptfa + iFA + Propolis (PFP) significantly increased (P<0.05). Likewise, Interleukin-2 (IL-2) and Interferon-y (IFN-y) cytokines in group Ptfa + iFA + Met20 µg·mL-1 (PFM20) and Ptfa + iFA + Propolis (PFP) were significantly higher than those of the other three experimental groups (P<0.05). The stimulation index (SI) value in chickens of group PFM20 was significantly higher than that of the other four experimental groups (P<0.05). Chickens that received MetII adjuvanted vaccinations benefitted from higher protection rate (88%) when challenged with Pasteurella multocida (P. multocida), which was significantly higher than those of group PF and PFP (P<0.05). These results suggested that the antimicrobial peptide MetII may play an adjuvant role in the immune response in chickens but need a proper usage, because the higher usage of 40 µg·mL-1 and 60 µg·mL-1 resulted poor effect. Whether MetII could be a potential adjuvant or a biomolecule as part of a complex adjuvant for vaccines needs more experimental evidence, the study still provides an examples for understanding vaccine adjuvants. [ABSTRACT FROM AUTHOR]

An effective vaccine that can protect against HIV infection does not exist. A major reason why a vaccine is not available is the high mutability of the virus, which enables it to evolve mutations that can evade human immune responses. This challenge is exacerbated by the ability of the virus to evolve compensatory mutations that can partially restore the fitness cost of immune-evading mutations. Based on the fitness landscapes of HIV proteins that account for the effects of coupled mutations, we designed a single long peptide immunogen comprising parts of the HIV proteome wherein mutations are likely to be deleterious regardless of the sequence of the rest of the viral protein. This immunogen was then stably expressed in adenovirus vectors that are currently in clinical development. Macaques immunized with these vaccine constructs exhibited T-cell responses that were comparable in magnitude to animals immunized with adenovirus vectors with whole HIV protein inserts. Moreover, the T-cell responses in immunized macaques strongly targeted regions contained in our immunogen. These results suggest that further studies aimed toward using our vaccine construct for HIV prophylaxis and cure are warranted.

The unprecedented global impact caused by SARS-CoV-2 imposed huge health and economic challenges, highlighting the urgent need for safe and effective vaccines. The receptor-binding domain (RBD) of SARS-CoV-2 is the major target for neutralizing antibodies and for vaccine formulations. Nonetheless, the low immunogenicity of the RBD requires the use of alternative strategies to enhance its immunological properties. Here, we evaluated the use of a subunit vaccine antigen generated after the genetic fusing of the RBD with a mouse IgG antibody. Subcutaneous administration of RBD-IgG led to the extended presence of the protein in the blood of immunized animals and enhanced RBD-specific IgG titers. Furthermore, RBD-IgG immunized mice elicited increased virus neutralizing antibody titers, measured both with pseudoviruses and with live original (Wuhan) SARS-CoV-2. Immunized K18-hACE2 mice were fully resistant to the lethal challenge of the Wuhan SARS-CoV-2, demonstrated by the control of body-weight loss and virus loads in their lungs and brains. Thus, we conclude that the genetic fusion of the RBD with an IgG molecule enhanced the immunogenicity of the antigen and the generation of virus-neutralizing antibodies, supporting the use of IgG chimeric antigens as an approach to improve the performance of SARS-CoV-2 subunit vaccines.

The purpose of this review was to analyze the findings of domestic and foreign researchers on the development of modern drugs for the specific prevention of plague and to illustrate the possibilities of using bioinformatics analysis at the design stages to create an effective and safe vaccine. Work on the creation of an effective new-generation plague vaccine is hampered by several factors associated primarily with the presence of mechanisms of evasion from the immune system of the macroorganism, as well as a large number of pathogenicity determinants in the plague agent. Due to the development of approaches that are based on in silico studies, there is a progressive development of vaccine technologies oriented primarily to the use of the most important immunogens of the plague microbe (F1 and V antigen). Studies aimed at improving the antigenic properties of F1 and LcrV, as well as work on bioinformatic search and analysis of additional promising components to be included in the composition of subunit vaccines are considered as topical applications of bioinformatics data analysis in developing the tools for enhancing the effectiveness of protection through vaccination with subunit preparations.

Antigens incorporated in subunit vaccines are typically poorly immunogenic, so a strong immunostimulant (adjuvant) and/or delivery system is required to boost immunogenicity. In this work, the various functional polymer nanostructures, that is, rods, worms, spheres, and tadpoles are used to develop potent peptide antigen delivery systems. The antigen PADRE-J8 (PJ8), derived from Group A Streptococcus (GAS) M-protein, is either physically mixed or chemically conjugated to polymeric nanoparticles of different shapes. The physical mixture of polymeric nanoparticles and antigen is more effective in inducing antibody production than their chemical conjugates. Moreover, rod-shaped polymeric nanoparticles in physical mixture with PJ8 elicited higher and more opsonic antibody titers than powerful complete Freund's adjuvant (CFA)-adjuvanted antigen. Herein, for the first time it is demonstrated that a) the block copolymer, in nanoparticle form, can act as an immune adjuvant, b) nanoparticle shape plays a crucial role in their immunogenicity, and c) antigen conjugation is not required, nor is antigen encapsulation or absorption. [ABSTRACT FROM AUTHOR]

Introduction: In the present study we evaluated the features of different recombinant forms of Zika virus (ZIKV) proteins produced in either bacterial (Eschericha coli) or insect cells (Drosophila melanogaster). The ZIKV-envelope glycoprotein (EZIKV) is responsible for virus entry into host cells, is the main target of neutralizing antibodies and has been used as a target antigen either for serological tests or for the development of subunit vaccines. The EZIKV is composed of three structural and functional domains (EDI, EDII, and EDIII), which share extensive sequence conservation with the corresponding counterparts expressed by other flaviviruses, particularly the different dengue virus (DENV) subtypes. Methods: In this study, we carried out a systematic comparison of the antigenicity and immunogenicity of recombinant EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells. For the antigenicity analysis we collected 88 serum samples from ZIKV-infected participants and 57 serum samples from DENV-infected. For immunogenicity, C57BL/6 mice were immunized with two doses of EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells to evaluate humoral and cellular immune response. In addition, AG129 mice were immunized with EZIKV and then challenge with ZIKV. Results: Testing of samples collected from ZIKV-infected and DENV-infected participants demonstrated that the EZIKV and EDIIIZIKV produced in BL21 cells presented better sensitivity and specificity compared to proteins produced in S2 cells. In vivo analyses were carried out with C57BL/6 mice and the results indicated that, despite similar immunogenicity, antigens produced in S2 cells, particularly EZIKV and EDIIIZIKV, induced higher ZIKV-neutralizing antibody levels in vaccinated mice. In addition, immunization with EZIKV expressed in S2 cells delayed the onset of symptoms and increased survival rates in immunocompromised mice. All recombinant antigens, either produced in bacteria or insect cells, induced antigen-specific CD4+ and CD8+ T cell responses. Conclusion: In conclusion, the present study highlights the differences in antigenicity and immunogenicity of recombinant ZIKV antigens produced in two heterologous protein expression systems. [ABSTRACT FROM AUTHOR]

(1) Background: Avian influenza has attracted widespread attention because of its severe effect on the poultry industry and potential threat to human health. The H9N2 subtype of avian influenza viruses was the most prevalent in chickens, and there are several commercial vaccines available for the prevention of the H9N2 subtype of avian influenza viruses. However, due to the prompt antigenic drift and antigenic shift of influenza viruses, outbreaks of H9N2 viruses still continuously occur, so surveillance and vaccine updates for H9N2 subtype avian influenza viruses are particularly important. (2) Methods: In this study, we constructed a stable Chinese hamster ovary cell line (CHO) to express the H9 hemagglutinin (HA) protein of the major prevalent H9N2 strain A/chicken/Daye/DY0602/2017 with genetic engineering technology, and then a subunit H9 avian influenza vaccine was prepared using the purified HA protein with a water-in-oil adjuvant. (3) Results: The results showed that the HI antibodies significantly increased after vaccination with the H9 subunit vaccine in specific-pathogen-free (SPF) chickens with a dose–dependent potency of the immunized HA protein, and the 50 μg or more per dose HA protein could provide complete protection against the H9N2 virus challenge. (4) Conclusions: These results indicate that the CHO expression system could be a platform used to develop the subunit vaccine against H9 influenza viruses in chickens.

ABSTRACT Over the past 150 years, vaccines have revolutionized the relationship between people and disease. During the COVID-19 pandemic, technologies such as mRNA vaccines have received attention due to their novelty and successes. However, more traditional vaccine development platforms have also yielded important tools in the worldwide fight against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A variety of approaches have been used to develop COVID-19 vaccines that are now authorized for use in countries around the world. In this review, we highlight strategies that focus on the viral capsid and outwards, rather than on the nucleic acids inside. These approaches fall into two broad categories: whole-virus vaccines and subunit vaccines. Whole-virus vaccines use the virus itself, in either an inactivated or an attenuated state. Subunit vaccines contain instead an isolated, immunogenic component of the virus. Here, we highlight vaccine candidates that apply these approaches against SARS-CoV-2 in different ways. In a companion article (H. M. Rando, R. Lordan, L. Kolla, E. Sell, et al., mSystems 8:e00928-22, 2023, https://doi.org/10.1128/mSystems.00928-22), we review the more recent and novel development of nucleic acid-based vaccine technologies. We further consider the role that these COVID-19 vaccine development programs have played in prophylaxis at the global scale. Well-established vaccine technologies have proved especially important to making vaccines accessible in low- and middle-income countries. Vaccine development programs that use established platforms have been undertaken in a much wider range of countries than those using nucleic acid-based technologies, which have been led by wealthy Western countries. Therefore, these vaccine platforms, though less novel from a biotechnological standpoint, have proven to be extremely important to the management of SARS-CoV-2. IMPORTANCE The development, production, and distribution of vaccines is imperative to saving lives, preventing illness, and reducing the economic and social burdens caused by the COVID-19 pandemic. Vaccines that use cutting-edge biotechnology have played an important role in mitigating the effects of SARS-CoV-2. However, more traditional methods of vaccine development that were refined throughout the 20th century have been especially critical to increasing vaccine access worldwide. Effective deployment is necessary to reducing the susceptibility of the world’s population, which is especially important in light of emerging variants. In this review, we discuss the safety, immunogenicity, and distribution of vaccines developed using established technologies. In a separate review, we describe the vaccines developed using nucleic acid-based vaccine platforms. From the current literature, it is clear that the well-established vaccine technologies are also highly effective against SARS-CoV-2 and are being used to address the challenges of COVID-19 globally, including in low- and middle-income countries. This worldwide approach is critical for reducing the devastating impact of SARS-CoV-2.

IntroductionIn the present study we evaluated the features of different recombinant forms of Zika virus (ZIKV) proteins produced in either bacterial (Eschericha coli) or insect cells (Drosophila melanogaster). The ZIKV-envelope glycoprotein (EZIKV) is responsible for virus entry into host cells, is the main target of neutralizing antibodies and has been used as a target antigen either for serological tests or for the development of subunit vaccines. The EZIKV is composed of three structural and functional domains (EDI, EDII, and EDIII), which share extensive sequence conservation with the corresponding counterparts expressed by other flaviviruses, particularly the different dengue virus (DENV) subtypes.MethodsIn this study, we carried out a systematic comparison of the antigenicity and immunogenicity of recombinant EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells. For the antigenicity analysis we collected 88 serum samples from ZIKV-infected participants and 57 serum samples from DENV-infected. For immunogenicity, C57BL/6 mice were immunized with two doses of EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells to evaluate humoral and cellular immune response. In addition, AG129 mice were immunized with EZIKV and then challenge with ZIKV.ResultsTesting of samples collected from ZIKV-infected and DENV-infected participants demonstrated that the EZIKV and EDIIIZIKV produced in BL21 cells presented better sensitivity and specificity compared to proteins produced in S2 cells. In vivo analyses were carried out with C57BL/6 mice and the results indicated that, despite similar immunogenicity, antigens produced in S2 cells, particularly EZIKV and EDIIIZIKV, induced higher ZIKV-neutralizing antibody levels in vaccinated mice. In addition, immunization with EZIKV expressed in S2 cells delayed the onset of symptoms and increased survival rates in immunocompromised mice. All recombinant antigens, either produced in bacteria or insect cells, induced antigen-specific CD4+ and CD8+ T cell responses.ConclusionIn conclusion, the present study highlights the differences in antigenicity and immunogenicity of recombinant ZIKV antigens produced in two heterologous protein expression systems.

During the COVID-19 pandemic, the development of prophylactic vaccines, including those based on new platforms, became highly relevant. One such platform is the creation of vaccines combining DNA and protein components in one construct. For the creation of DNA vaccine, we chose the full-length spike protein (S) of the SARS-CoV-2 virus and used the recombinant receptor-binding domain (RBD) of the S protein produced in CHO-K1 cells as a protein component. The immunogenicity of the developed combined vaccine and its individual components was compared and the contribution of each component to the induction of the immune response was analyzed. The combined DNA/protein vaccine possesses the advantages of both underlying approaches and is capable of inducing both humoral (similar to subunit vaccines) and cellular (similar to DNA vaccines) immunity. [ABSTRACT FROM AUTHOR]

Optimal exposure and interaction of subunit antigens with the immune system are crucial for effective immunity. The epidermis and dermis, which harbor a significant population of antigen-presenting cells (APCs) and are broadly connected to the lymphatic system, serve as ideal sites for immunization to fulfill these objectives. However, the stratum corneum barrier severely hinders transdermal delivery of antigens. Here, we developed a transdermal platform integrating yeast-derived biomimetic glucan particles (GPs) and polymeric microneedles to overcome the hurdles and induce effective immunity. GPs served as carriers for encapsulating antigens in a pathogen-like manner. The antigen-loaded particles were concentrated within the tips of polymeric microneedle to solidify as tiny reservoirs, while the needle bodies were shaped using a fast-dissolving matrix. This tip-loaded approach enabled rapid administration for better compliance, followed by an extended antigen release at administration sites, aiming for recruiting more APCs. This microscale platform capacitated a multi-functional approach for subunit vaccine development by optimizing both delivery carriers and dosage forms with modulated release mechanisms to enhance antigen exposure and interaction, thereby promoting effective humoral and cellular immunity. [Display omitted] • The integration of glucan particles and polymeric microneedles enhances immune effects of subunit vaccines. • A tip-loaded approach in microneedle fabrication allows rapid administration while facilitating extended antigen release. • Amplified antigen exposure and antigen interaction with the immune system unlock the gateway to robust immune responses. • A microscale transdermal platform integrating multifunctional strategies ensures generalizability in delivering subunit antigens. [ABSTRACT FROM AUTHOR]

In December 2019, cases of atypical pneumonia were diagnosed in hospital patients in Wuhan, Hubei province, China. The disease, now known as COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As case numbers increased and spread across the planet many companies scrambled to develop vaccines to control the infection and disease. Prior research on SARS-CoV-1, new vaccine technologies and unprecedented funding have allowed vaccines to be developed and approved in record time, without the usual pauses and bypassing any of the requirements of the vaccine approval process. This paper is a review of the current literature on some of the vaccines targeting SARS-CoV-2 and of the new technologies used to produce them.

The main triggers of new infectious diseases, including those with pandemic potential, are: spontaneous emergence of infectious strains which are more virulent for humans and contribute to transmission of pathogenic microorganisms, environmental changes, social and economic factors, increased contact rates between different regions. A successful pandemic response requires mass immunisation against a specific disease, aimed at the development of herd immunity which is based on the concept of indirect protection of the whole of the population by immunising a part of it. A well-grounded choice of the vaccine platform is central to dealing with this problem. The aim of the study was to compare characteristics of vaccine platforms (attenuated, inactivated, subunit, recombinant vector, DNA, and RNA vaccines) intended for mass immunisation against dangerous and extremely dangerous viral infections with pandemic potential. The study focused on the members of Poxviridae, Orthomyxoviridae and Coronaviridae families as potential pathogens. The vaccine platforms were compared in terms of the following parameters: capability of producing a robust immune response; protective efficacy; time required for vaccine development and testing; ability to produce vaccine in volumes required for mass immunisation; potential obstacles associated with the intended use of the vaccine. It is expected that in the next few decades DNA and RNA vaccine platforms will be most widely used for development of products against dangerous and extremely dangerous viral infections with pandemic potential, regardless of taxonomic groups of pathogens.

Major capsid protein (MCP) can be used as a subunit vaccine against largemouth bass virus (LMBV). However, subunit vaccines usually have low immunogenicity. Here, to identify the major immunogenicity determinant region of the MCP gene, we truncated the MCP of the LMBV gene into four parts (MCP‐1, MCP‐2, MCP‐3 and MCP‐4). Enzyme‐linked immunosorbent assay (ELISA) was used to identify the antigenicity of these four truncated MCP proteins. Then, the highly antigenic truncated protein was modified with mannose and connected with functionalized single‐walled carbon nanotubes (SWCNTs) as carriers. Largemouth basses were immunized by bath immersion, challenged with LMBV on the 28th day after immunization and evaluated for related immune indicators. The results indicated that the MCP‐2 protein could induce a higher antibody titre than the other truncated MCP proteins. We found that the levels of immune‐related genes (TNF‐α, CD40, IgM, IFNγ and IL‐10) in the spleen and kidney were significantly increased in the MCP‐2 and MCP‐2‐Man groups. ELISA results showed that the antibody content in the serum increased significantly in the MCP‐2 group 7 days post‐vaccination and increased with days in all the vaccinated groups, with the highest observed on the 21st day. Notably, the MCP‐2‐Man vaccine (10 mg L−1) showed durability of immunoprotection efficacy that could protect largemouth basses from LMBV challenge, and the immune protection rate reached 78.94%. These results suggest that MCP‐2 might be the major immunogenicity determinant region of LMBV and that the mannose‐modified MCP‐2 vaccine can induce stronger adaptive immune responses. [ABSTRACT FROM AUTHOR]

• Live vaccines can deliver antigens to mucosal surfaces. • Immunogenicity of live vaccines can be improved with immunomodulatory proteins. • Immune modulation induces inflammatory, antibody, or cell-mediated responses. • Live vaccines can be augmented to strengthen innate and adaptive immune responses. • Co-delivery of immunomodulatory proteins can enhance ethe efficacy of live vaccines. Vaccines are very effective in providing protection against many infectious diseases. However, it has proven difficult to develop highly efficacious vaccines against some pathogens and so there is a continuing need to improve vaccine technologies. The first successful and widely used vaccines were based on attenuated pathogens (e.g., laboratory passaged Pasteurella multocida to vaccinate against fowl cholera) or closely related non-pathogenic organisms (e.g., cowpox to vaccinate against smallpox). Subsequently, live vaccines, either attenuated pathogens or non-pathogenic microorganisms modified to deliver heterologous antigens, have been successfully used to induce protective immune responses against many pathogens. Unlike conventional killed and subunit vaccines, live vaccines can deliver antigens to mucosal surfaces in a similar manner and context as the natural infection and hence can often produce a more appropriate and protective immune response. Despite these advantages, there is still a need to improve the immunogenicity of some live vaccines. The efficacy of injectable killed and subunit vaccines is usually enhanced using adjuvants such mineral salts, oils, and saponin, but such adjuvants cannot be used with live vaccines. Instead, live vaccines can be engineered to produce immunomodulatory molecules that can stimulate the immune system to induce more robust and long-lasting adaptive immune responses. This review focuses on research that has been undertaken to engineer live vaccines to produce immunomodulatory molecules that act as adjuvants to increase immunogenicity. Adjuvant strategies with varying mechanisms of action (inflammatory, antibody-mediated, cell-mediated) and delivery modes (oral, intramuscular, intranasal) have been investigated, with varying degrees of success. The goal of such research is to define adjuvant strategies that can be adapted to enhance live vaccine efficacy by triggering strong innate and adaptive immune responses and produce vaccines against a wider range of pathogens. [ABSTRACT FROM AUTHOR]

Subunit vaccines, significant in next-generation vaccine development, offer precise targeting of immune responses by focusing on specific antigens. However, this precision often comes at the cost of eliciting strong and durable immunity, posing a great challenge to vaccine design. To address this limitation, recent advancements in nanoparticles (NPs) are utilized to enhance antigen delivery efficiency and boost vaccine efficacy. This review examines how the physicochemical properties of NPs influence various stages of the immune response during vaccine delivery and analyzes how different NP types contribute to immune activation and enhance vaccine performance. It then explores the unique characteristics and immune activation mechanisms of these NPs, along with their recent advancements, and highlights their application in subunit vaccines targeting infectious diseases and cancer. Finally, it discusses the challenges in NP-based vaccine development and proposes future directions for innovation in this promising field., (© 2024 Wiley‐VCH GmbH.)

African Swine Fever (ASF) is an acute, highly contagious, and lethal disease caused by the African Swine Fever Virus (ASFV), posing a severe threat to the global pig farming industry. Although live vaccines are currently available, preventing and controlling ASF remains a considerable challenge. Several factors have impeded vaccine development, including the complexity of ASFV particles and the suppressive effects of its gene-encoded proteins on the host's immune system. This article delves into the immunological responses elicited by ASFV, encompassing both innate and adaptive immunity, and examines how ASFV evades host immune defenses. Special attention is given to the current progress in the development of ASFV subunit vaccines, including protein-based vaccines, DNA vaccines, and viral vector vaccines. The advantages, challenges, and future directions of different vaccine types are discussed, offering new perspectives and insights for the future of ASFV vaccine development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Mpox (formerly known as monkeypox), which has symptoms similar to smallpox, is a zoonotic disease caused by the monkeypox virus (MPXV). From 1 January 2022 to 31 March 2024, 117 countries, territories, or areas reported 95,226 laboratory-confirmed cases of Mpox (including 185 deaths) to the World Health Organization. However, as there is no licensed specific MPXV vaccine available globally, the vaccines currently used for mpox prevention are mostly smallpox vaccines. Thus, the rapid development of safe and effective vaccines is urgently required. In the present study, the key MPXV proteins A35, B6R, E8L, A29, M1R, and H3L were expressed and prepared using a prokaryotic expression system (Escherichia coli) and a eukaryotic expression system (yeast), and the fusion antigens A35-A29 and A35-M1R were constructed based on the dimerization characteristics of the A35 protein. By combining the antigens with aluminum hydroxide and CpG adjuvants in different combinations, we developed nine multicomponent MPXV subunit vaccine candidates. Each antigen (10 μg) and fusion antigen (20 μg) were used to immunize the mice. The first two doses produced a mean titer of 10(Petersen et al., 2016 [5] ) , and the third dose maintained the same potent antibody-specific response as the previous two immunizations. The protective activity of different antigen combinations was determined using the cell neutralization test of vaccinia virus (VACV), which showed that the subunit vaccine candidates with two to six components (MPXV6/5/4/3a/3b/Fa/2a) had good neutralizing activity, and antigens A35 and M1R could produce neutralizing antibodies against VACV. The neutralizing antibody titer of the fusion antigen MPXVFa (A35-M1R), detected 2 weeks after the second booster dose, was comparable with that of MPXV2a (A35 and M1R). The A35-M1R fusion protein not only provided a high level of protection as a protective antigen but also simplified the preparation of candidate antigens. In summary, we systematically investigated the different protective antigen candidates of MPXV that have been widely studied and provided critical insights into the key protective antigen composition for vaccines, thus establishing a technical and theoretical foundation for the development of MPXV subunit vaccines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The pandemic of the new coronavirus (COVID-19) disease that began in December 2019 in China is still having a huge impact on all spheres of human life. The herd immunity, which is the most effective tool for preventing the spread of the disease, is formed in two ways: the passive way (i.e., the formation of a population not susceptible to re-infection due to the natural spread of the disease) and the active way (mass immunisation). High rates of COVID-19 vaccination were achieved thanks to the development and mass production of new vaccines. The selection of the most promising vaccine platforms is one of the key aspects of successful mass immunisation. The aim of the study was to compare the characteristics of COVID-19 vaccines used for mass immunisation. The paper analyses the vaccine technology platforms, efficacy of different types of vaccines based on clinical trial results, safety of vaccines for different population groups, and potential for scaling up vaccine production in order to ensure the necessary vaccination coverage. The vaccines currently used for mass immunisation are: BNT162b2 (Pfizer/BioNTech), mRNA1273 (Moderna), Gam-COVID-Vac (N.F. Gamaleya National Research Center for Epidemiology and Microbiology), Ad26.COV2.S (Johnson & Johnson), ChAdOx1-S (AZD1222) (AstraZeneca), BBIBP-CorV (Sinopharm), CoronaVac (Sinovac Biotech), and NVX-CoV2373 (Novavax). The comparison of the main characteristics of the vaccines demonstrated that the most promising types of vaccines for COVID-19 specific prophylaxis are RNA vaccines and recombinant adenovirus vector-based vaccines.

Pseudorabies (PR), which is caused by the pseudorabies virus (PRV), is a severe infectious disease that causes abortions in adult sows and fatal encephalitis in piglets; the disease can occur in pigs of all ages and other mammals, which can lead to significant economic loss around the worldwide. The new PRV variant invalidated the available commercial attenuated and inactivated vaccines. Consequently, subunit vaccines have been suggested as novel strategies for PR control, while they are usually formulated with adjuvants due to their lower immunogenicity. We aimed to select a safe and efficient adjuvant for subunit vaccines for PR. In our study, glycoprotein B (gB) and glycoprotein D (gD) were expressed based on a baculovirus expression system, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was expressed using an Escherichia coli (E. coli) expression system; subsequently, a gB + gD subunit vaccine adjuvanted by GM-CSF was constructed. A rabbit model infected with a PRV SD-2017 strain was established, the TCID50 and LD50 were measured, and the typical clinical symptoms were observed. After a lethal challenge of 5 LD50 with a PRV SD-2017 strain, the rabbits exhibited typical clinical symptoms, including itching and high temperature, and histopathology revealed severe inflammation in the brain, which is the dominant target organ of PRV. Rabbits immunized with the gB + gD + GM-CSF subunit vaccines produced higher levels of antibodies than those immunized with gB + gD + ISA 201, which was adjuvanted with a frequently used oil adjuvant. The survival rate of rabbits vaccinated with gB + gD + GM-CSF was 100%, which was superior to that of rabbits vaccinated with gB + gD + ISA 201 (80%), inactivated PRV + GM-CSF (60%) and commercial inactivated vaccine (60%) after challenge with PRV SD-2017. These data suggested that the gB + gD + GM-CSF-based subunit vaccine had good protective efficacy against the PRV SD-2017 strain in rabbits and that GM-CSF could be developed as a candidate adjuvant for use in a vaccine regimen to prevent and even eradicate PR. [ABSTRACT FROM AUTHOR]

Viral subunit vaccines are a safer and more tolerable alternative to whole inactivated virus vaccines. However, they often come with limited efficacy, necessitating the use of adjuvants. Using free and particle-bound viral antigens, we assessed whether size affects the uptake of those antigens by human monocyte-derived dendritic cells (Mo-DCs) and whether differences in uptake affect their capacity to stimulate cytokine production by T cells. To this end, influenza antigens and hepatitis B surface antigen (HBsAg) were covalently conjugated to polystyrene particles of 500 nm and 3 μm. Cellular uptake of the antigens, either unconjugated or conjugated, and their capacity to stimulate T cells within a population of human peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry. Conjugation of both antigens to particles significantly increased their uptake by Mo-DCs. Moreover, both the 500 nm and 3 μm influenza conjugates induced significantly higher numbers of cytokine-producing CD4+ T cells and induced increased production of the pro-inflammatory cytokines IFNγ and TNFα. In contrast, conjugation of HBsAg to particles did not notably affect the T cell response. In conclusion, conjugation of antigen to 500 nm and 3 μm particles leads to increased antigen uptake by human Mo-DCs, although the capacity of such conjugates to induce T cell stimulation likely depends on the immunological status of the PBMC donor. [ABSTRACT FROM AUTHOR]

Viral subunit vaccines often suffer low efficacy. We recently showed that when taken out of the context of whole virus particles, recombinant subunit vaccines contain artificially exposed surface regions that are non-neutralizing and reduce their efficacy, and thus these regions need to be re-buried in vaccine design. Here we used the envelope protein domain III (EDIII) of Japanese encephalitis virus (JEV), a subunit vaccine candidate, to further validate this important concept for subunit vaccine designs. We constructed monomeric EDIII, dimeric EDIII via a linear space, dimeric EDIII via an Fc tag, and trimeric EDIII via a foldon tag. Compared to monomeric EDIII or linearly linked dimeric EDIII, tightly packed EDIII oligomers via the Fc or foldon tag induce higher neutralizing antibody titers in mice and also protect mice more effectively from lethal JEV challenge. Structural analyses demonstrate that part of the artificially exposed surface areas on recombinant EDIII becomes re-buried in Fc or foldon-mediated oligomers. This study further establishes the artificially exposed surfaces as an intrinsic limitation of subunit vaccines, and suggests that re-burying these surfaces through tightly packed oligomerization is a convenient and effective approach to overcome this limitation. [ABSTRACT FROM AUTHOR]