Ideal Vaccine Research Articles

TianTan vaccinia virus-based EBV vaccines targeting both latent and lytic antigens elicits potent immunity against lethal EBV challenge in humanized mice

ABSTRACT Epstein–Barr virus (EBV) infection has been related to multiple epithelial cancers and lymphomas. Current efforts in developing a prophylactic EBV vaccine have focused on inducing neutralizing antibodies. However, given the lifelong and persistent nature of EBV infection following primary infection, it is rationalized that an ideal vaccine should elicit both humoral and cellular immune responses targeting multiple stages of the EBV lifecycle. This study used a DNA vector and a TianTan vaccinia virus to express key EBV antigens, including BZLF1, EBNA1, EBNA3B, and gH/gL, to generate multi-antigen vaccines. The multi-antigen vaccine expressing all four antigens and the multi-antigen vaccine expressing BZLF1, EBNA1, and EBNA3B showed comparable protection effects and prevented 100% and 80% of humanized mice, respectively, from EBV-induced fatal B cell lymphoma by activating BZLF1, EBNA1, and EBNA3B specific T cell. The vaccine expressing lytic protein BZLF1 elicited stronger T cell responses and conferred superior protection compared to vaccines targeting single latent EBNA1 or EBNA3B. The vaccine solely expressing gH/gL exhibited no T cell protective effects in our humanized mice model. Our study implicates the potential of EBV vaccines that induce potent cellular responses targeting both latent and lytic phases of the EBV life cycle in the prevention of EBV-induced B cell lymphoma.

Advances in Leishmania Vaccines: Current Development and Future Prospects.

Leishmaniasis is a neglected tropical disease caused by parasites of the genus Leishmania. As approved human vaccines are not available, treatment and prevention rely heavily on toxic chemotherapeutic agents, which face increasing resistance problems. The development of effective vaccines against human leishmaniasis is of utmost importance for the control of the disease. Strategies that have been considered for this purpose range from whole-killed and attenuated parasites to recombinant proteins and DNA vaccines. The ideal vaccine must be safe and effective, ensuring lasting immunity through a robust IL-12-driven Th1 adaptive immune response. Despite some success and years of effort, human vaccine trials have encountered difficulties in conferring durable protection against Leishmania, a problem that may be attributed to the parasite's antigenic diversity and the intricate nature of the host's immune response. The aim of this review is to provide a thorough overview of recent advances in Leishmania vaccine development, ranging from initial trials to recent achievements, such as the ChAd63-KH DNA vaccine, which underscores the potential for effective control of leishmaniasis through continued research in this field.

Strategies and Techniques for Enhancing Fish Health and Averting Disease Outbreaks in Aquaculture Settings through the Use of Vaccination: A Review

The fastest–growing animal food-producing agricultural sector in the world is aquaculture, which accounts for almost half of the world’s food fish production.However, the expansion of high-density fish populations also brings forth a challenge–the rapid transmission and spread of infectious agents including several viral, bacterial, and parasitic diseases. Expansion and successful development of sustainable aquaculture practice and increasing production largely depends upon the prevention and control of outbreaks of several emerging and re-emerging infectious diseases which can result in economic loss, food safety hazards, and environmental hazards. Vaccination strategies have become highly effective and economical in protecting the health of fish and other aquaculture organisms from various infectious diseases such as edwardsiellosis, motile aeromonas septicemia (MAS), Tilapia Lake Virus (TiLV) disease, infectious salmon anemia (ISA), vibriosis, and white spot disease etc. An ideal vaccine is expected to be safe, effective, economical, and easily administered. Most of the available fish vaccines are empirically designed vaccines based on inactivated or live attenuated bacterin vaccines. Novel advances in the fields of immunology, biotechnology, and molecular biology have led to the development in designing novel and effective fish vaccines and the improvement of the existing vaccines to provide sufficient immune protection against diseases. This review investigates the currently available fish vaccines for use in finfish aquaculture against different infectious diseases different mode of vaccine administration with addressing pros and cons in detail. The information was collected from different secondary sources, and then compiled systematically.

Empowering pharmacy technicians as vaccine champions: A pilot study in independent community pharmacies

BackgroundIncreasing vaccine uptake in communities has been essential, even before coronavirus disease 2019. The use of "vaccine champions" or "VaxChamps" has shown promise. VaxChamps, who are often community members with specialized training but no special credentials, advocate for vaccination by sharing their experiences and knowledge. Pharmacy technicians’ scope of practice, coupled with their frequent interactions with pharmacy patients, make them ideal vaccine champions and a natural fit for the VaxChamp program. This study assessed the implementation and impact of the VaxChamp program in North Dakota community pharmacies. ObjectivesTo describe the development and implementation of the VaxChamp program in community pharmacies and evaluate its effect on vaccination rates and vaccine-related tasks within each pharmacy’s organizational context. MethodsThe VaxChamp program involved training one technician per participating pharmacy to spend 5 hours per week on vaccine-related tasks. Data collection included pre-post surveys, monthly reports, and semi-structured interviews with VaxChamps and pharmacists-in-charge from 6 pharmacies. Quantitative data were analyzed using descriptive statistics, while qualitative data were analyzed using inductive methods to identify key themes. ResultsThe 6 participating pharmacies varied in location and staffing. Most had prior vaccine administration experience. VaxChamps’ roles ranged from administrative tasks to direct vaccine administration, depending on the pharmacy’s staffing and workflow. Vaccination rates for pneumococcal and hepatitis B vaccines increased in several pharmacies, while shingles vaccination rates declined. The presence of advanced pharmacy practice experience students often influenced VaxChamps’ responsibilities, underscoring the need for clear role delineation. ConclusionIntegrating pharmacy technicians as VaxChamps in community pharmacies is a promising strategy to increase vaccination rates and enhance public health. Future research should explore ways to better integrate technicians into comprehensive immunization strategies and address the contextual factors that influence program implementation.

Preparation and immunological activity evaluation of an intranasal protein subunit vaccine against ancestral and mutant SARS-CoV-2 with curdlan sulfate/O-linked quaternized chitosan nanoparticles as carrier and adjuvant

Chitosan and its derivatives are ideal nasal vaccine adjuvant to deliver antigens to immune cells. Previously, we successfully used a chitosan derivative, O-(2-Hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (O-HTCC), and a β-glucan derivative, curdlan sulfate (CS), to prepare a nanoparticle adjuvant CS/O-HTCC which could deliver ovalbumin to antigen presenting cells (APCs) through nasal inhalation. In this article, we used SARS-CoV-2 spike receptor binding domain (S-RBD) as the antigen and CS/O-HTCC nanoparticles as the adjuvant to develop a nasal mucosal protein subunit vaccine, CS/S-RBD/O-HTCC. The humoral immunity, cell-mediated immunity and mucosal immunity induced by vaccines were evaluated. The results showed that CS/S-RBD/O-HTCC could induce desirable immunization with single or bivalent antigen through nasal inoculation, giving one booster vaccination with mutated S-RBD (beta) could bring about a broad cross reaction with ancestral and different mutated S-RBD, and vaccination of the BALB/c mice with CS/S-RBD/O-HTCC containing S-RBD mix antigens (ancestral and omicron) could induce the production of binding and neutralizing antibodies against both of the two antigens. Our results indicate that CS/O-HTCC is a promising nasal mucosal adjuvant to prepare protein subunit vaccine for both primary and booster immunization, and the adjuvant is suitable for loading more than one antigen for preparing multivalent vaccines.

Advancements in Fish Vaccination: Current Innovations and Future Horizons in Aquaculture Health Management

Aquaculture is rapidly becoming one of the pivotal sectors in the farming economy, driven by the increasing demand for high-quality animal protein at an affordable cost, especially with the escalating human population. However, the expansion of high-density fish populations also brings forth a challenge—the rapid transmission and spread of infectious disease agents among them. To combat this, vaccination is emerging as a reliable and standardized method for providing immunity against viral and bacterial outbreaks. The ideal vaccine is expected to be safe, effective, economical, and easily administered. The fish vaccination industry continually publishes new information on fish immunology and vaccinology, contributing to the improvement in vaccine formulation and efficacy. This review aims to offer insights into the current status of bacterial, viral, and parasitic diseases, discuss existing vaccinations, and address potential industry-threatening diseases like infectious edwardsiellosis, motile aeromonas septicemia (MAS), Tilapia Lake Virus (TiLV) disease, infectious salmon anemia (ISA), vibriosis, and white spot disease. Technological advancements have played a crucial role in enhancing our understanding of fish immunological mechanisms, leading to improved vaccine administration and the development of recombinant live attenuated, subunit, DNA, and RNA vaccines. However, challenges such as oral tolerance, vaccine degradation, and stressful environments persist, impacting vaccine efficacy. Addressing these challenges and gaining a deeper understanding of the fish immune system and host–pathogen interactions will be pivotal for future improvements, contributing to the sustainability of aquaculture and enhancing global food security.

A gH/gL-encoding replicon vaccine elicits neutralizing antibodies that protect humanized mice against EBV challenge

Epstein-Barr virus (EBV) is associated with several malignancies, neurodegenerative disorders and is the causative agent of infectious mononucleosis. A vaccine that prevents EBV-driven morbidity and mortality remains an unmet need. EBV is orally transmitted, infecting both B cells and epithelial cells. Several virally encoded proteins are involved in entry. The gH/gL glycoprotein complex is essential for infectivity irrespective of cell type, while gp42 is essential for infection of B cells. gp350 promotes viral attachment by binding to CD21 or CD35 and is the most abundant glycoprotein on the virion. gH/gL, gp42 and gp350, are known targets of neutralizing antibodies and therefore relevant immunogens for vaccine development. Here, we developed and optimized the delivery of several alphavirus-derived replicon RNA (repRNA) vaccine candidates encoding gH/gL, gH/gL/gp42 or gp350 delivered by a cationic nanocarrier termed LION™. The lead candidate, encoding full-length gH/gL, elicited high titers of neutralizing antibodies that persisted for at least 8 months and a vaccine-specific CD8+ T cell response. Transfer of vaccine-elicited IgG protected humanized mice from EBV-driven tumor formation and death following high-dose viral challenge. These data demonstrate that LION/repRNA-gH/gL is an ideal candidate vaccine for preventing EBV infection and/or related malignancies in humans.

Exploration of chitosan and its modified derivatives as vaccine adjuvant: A review

Chitosan is a natural polysaccharide that has earned much credit in the pharmaceutical field due to its broad implementation in drugs, antigens, and vaccine delivery. Owing to unique characteristics of biocompatibility, biodegradability, mucoadhesiveness, and less toxicity, chitosan holds promise as a vaccine adjuvant or vaccine delivery system. Furthermore, chitosan exhibits antiviral properties making it an ideal vaccine adjuvant and carrier for the delivery of vaccine. The presence of ridiculous functional groups in the parent structure of chitosan enables the creation of modified chitosan derivatives having improved physiochemical properties which provide enhanced vaccine adjuvant properties of chitosan. This review summarizes the potential of chitosan and its modified derivatives as an antiviral agent and vaccine adjuvant along with patents related to the application of chitosan as a vaccine adjuvant and vaccine carrier.

Evaluation in mice of cell-free produced CT584 as a Chlamydia vaccine antigen.

Chlamydia trachomatis is the most prevalent bacterial sexually transmitted pathogen worldwide. Since chlamydial infection is largely asymptomatic with the potential for serious complications, a preventative vaccine is likely the most viable long-term answer to this public health threat. Cell-free protein synthesis (CFPS) utilizes the cellular protein manufacturing machinery decoupled from the requirement for maintaining cellular viability, offering the potential for flexible, rapid, and de-centralized production of recombinant protein vaccine antigens. Here, we use CFPS to produce the putative chlamydial type three secretion system (T3SS) needle-tip protein, CT584, for use as a vaccine antigen in mouse models. High-speed atomic force microscopy (HS-AFM) imaging and computer simulations confirm that CFPS-produced CT584 retains a native-like structure prior to immunization. Female mice were primed with CT584 adjuvanted with CpG-1826 intranasally (i.n.) or CpG-1826 + Montanide ISA 720 intramuscularly (i.m.), followed four-weeks later by an i.m. boost before respiratory challenge with 104 inclusion forming units (IFU) of Chlamydia muridarum. Immunization with CT584 generated robust antibody responses but weak cell mediated immunity and failed to protect against i.n. challenge as demonstrated by body weight loss, increased lungs' weights and the presence of high numbers of IFUs in the lungs. While CT584 alone may not be the ideal vaccine candidate, the speed and flexibility with which CFPS can be used to produce other potential chlamydial antigens makes it an attractive technique for antigen production.

Impact of gender and education on cervical cancer knowledge amongst students: implications for health policies and public health strategies in Wiesbaden, Germany.

Cervical cancer is a global health concern primarily caused by human papillomavirus (HPV). It has a significant impact in Germany, with thousands of new diagnoses and deaths annually. Despite advancements in screening and treatment leading to improved survival rates of 65% for invasive cervical tumors, the financial burden remains substantial. The study aims to assess the impact of gender and education of Wiesbaden students towards cervical cancer and its associated health policies. Data was collected through an online questionnaire distributed with 54 students in Wiesbaden, Germany participating in the study. Statistical analysis was performed using SPSS, including one-way ANOVA, t-tests, Kruskal-Wallis, and chi-square tests. The respondents' average age was 28.24 years, with a higher female participation. Education level did not significantly influence perceptions of ideal vaccination age (p < 0.581). Females and males perceived a lower number of vaccine doses (< 3) required compared to the standard. Education level showed a moderate association with knowledge of long-term complications, and gender had a moderate correlation with information sources (rho = 27, p = 0.090). Gender disparities did not significantly impact knowledge of cervical cancer. Public health programs should consider education levels and tailor interventions to all age groups and genders.

Untangling the stranglehold through mathematical modelling of Streptococcus equi subspecies equi transmission

Strangles, a disease caused by infection with Streptococccus equi subspecies equi (S. equi), is endemic worldwide and one of the most frequently diagnosed infectious diseases of horses. Recent work has improved our knowledge of key parameters of transmission dynamics, but important knowledge gaps remain. Our aim was to apply mathematical modelling of S. equi transmission dynamics to prioritise future research areas, and add precision to estimates of transmission parameters thereby improving understanding of S. equi epidemiology and quantifying the control effort required. A compartmental deterministic model was constructed. Parameter values were estimated from current literature wherever possible. We assessed the sensitivity of estimates for the basic reproduction number on the population scale to varying assumptions for the unknown or uncertain parameters of: (mean) duration of carriership (1∕γC), relative infectiousness of carriers (f), proportion of infections that result in carriership (p), and (mean) duration of immunity after natural infection (1∕γR). Available incidence and (sero-)prevalence data were compared to model outputs to improve point estimates and ranges for these currently unknown or uncertain transmission-related parameters. The required vaccination coverage of an ideal vaccine to prevent major outbreaks under a range of control scenarios was estimated, and compared available data on existing vaccines. The relative infectiousness of carriers (as compared to acutely ill horses) and the duration of carriership were identified as key knowledge gaps. Deterministic compartmental simulations, combined with seroprevalence data, suggest that 0.05<fˆ<0.5 and that the duration of protective immunity after infection is likely 4–6 years. The presence of carriers alone may suffice to keep S. equi endemic in a population, implying that carriers cannot be ignored in control efforts. Weekly screening of herds for signs of strangles could be sufficient to ensure R < 1, provided all horses are screened for carriership post-infection. In some of worst-case scenarios, vaccination alone would not suffice to prevent major outbreaks from occurring. A stochastic agent-based model was also constructed and validated, and used to simulate a remount depot, to evaluate whether historical incidence data of recurrence of strangles within individuals could be explained without the assumption that one in four horses fail to mount a lasting immune response. These simulations demonstrated that the observed data could have occurred without that assumption.

Immunoinformatics design of a structural proteins driven multi-epitope candidate vaccine against different SARS-CoV-2 variants based on fynomer

The ideal vaccines for combating diseases that may emerge in the future require more than simply inactivating a few pathogenic strains. This study aims to provide a peptide-based multi-epitope vaccine effective against various severe acute respiratory syndrome coronavirus 2 strains. To design the vaccine, a library of peptides from the spike, nucleocapsid, membrane, and envelope structural proteins of various strains was prepared. Then, the final vaccine structure was optimized using the fully protected epitopes and the fynomer scaffold. Using bioinformatics tools, the antigenicity, allergenicity, toxicity, physicochemical properties, population coverage, and secondary and three-dimensional structures of the vaccine candidate were evaluated. The bioinformatic analyses confirmed the high quality of the vaccine. According to further investigations, this structure is similar to native protein and there is a stable and strong interaction between vaccine and receptors. Based on molecular dynamics simulation, structural compactness and stability in binding were also observed. In addition, the immune simulation showed that the vaccine can stimulate immune responses similar to real conditions. Finally, codon optimization and in silico cloning confirmed efficient expression in Escherichia coli. In conclusion, the fynomer-based vaccine can be considered as a new style in designing and updating vaccines to protect against coronavirus disease.

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.

How the Timing of Annual COVID-19 Vaccination of Nursing Home Residents and Staff Affects Its Value

ObjectivesTo evaluate the epidemiologic, clinical, and economic value of an annual nursing home (NH) COVID-19 vaccine campaign and the impact of when vaccination starts. DesignAgent-based model representing a typical NH. Setting and ParticipantsNH residents and staff. MethodsWe used the model representing an NH with 100 residents, its staff, their interactions, COVID-19 spread, and its health and economic outcomes to evaluate the epidemiologic, clinical, and economic value of varying schedules of annual COVID-19 vaccine campaigns. ResultsAcross a range of scenarios with a 60% vaccine efficacy that wanes starting 4 months after protection onset, vaccination was cost saving or cost-effective when initiated in the late summer or early fall. Annual vaccination averted 102 to 105 COVID-19 cases when 30-day vaccination campaigns began between July and October (varying with vaccination start), decreasing to 97 and 85 cases when starting in November and December, respectively. Starting vaccination between July and December saved $3340 to $4363 and $64,375 to $77,548 from the Centers for Medicare & Medicaid Services and societal perspectives, respectively (varying with vaccination start). Vaccination's value did not change when varying the COVID-19 peak between December and February. The ideal vaccine campaign timing was not affected by reducing COVID-19 levels in the community, or varying transmission probability, preexisting immunity, or COVID-19 severity. However, if vaccine efficacy wanes more quickly (over 1 month), earlier vaccination in July resulted in more cases compared with vaccinating later in October. Conclusions and ImplicationsAnnual vaccination of NH staff and residents averted the most cases when initiated in the late summer through early fall, at least 2 months before the COVID-19 winter peak but remained cost saving or cost-effective when it starts in the same month as the peak. This supports tethering COVID vaccination to seasonal influenza campaigns (typically in September-October) for providing protection against SARS-CoV-2 winter surges in NHs.

Liposome-based dry powder vaccine immunization targeting the lungs induces broad protection against pneumococcus

Streptococcus pneumoniae is an important human pathogen. Currently used conjugate vaccines are effective against invasive disease, but protection is restricted to serotypes included in the formulation, leading to serotype replacement. Furthermore, protection against non-invasive disease is reported to be considerably lower. The development of a serotype-independent vaccine is thus important and Pneumococcal surface protein A (PspA) is a promising vaccine candidate. PspA shows some diversity and can be classified in 6 clades and 3 families, with families 1 and 2 being the most frequent in clinical isolates. The ideal vaccine should thus induce protection against the two most common families of PspA. The aim of this work was to develop a liposome-based vaccine containing PspAs from family 1 and 2 and to characterize its immune response. Liposomes (LP) composed of dipalmitoylphosphatidylcholine (DPPC) and 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol) with or without α-galactosylceramide (α-GalCer) were produced by microfluidics, encapsulating PspA from clade 1 (PspA1, family 1) and/or clade 4 (PspA4Pro, family 2) followed by spray-drying with trehalose to form nanocomposite microparticles carriers (NCMP). LP/NCMPs showed good stability and preservation of protein activity. LP/NCMPs containing PspA1 and/or PspA4Pro were used for immunization of mice targeting the lungs. High serum IgG antibody titers against both PspA1 and PspA4Pro were detected in animals immunized with LP/NCMPs containing α-GalCer, with a balance of IgG1 and IgG2a titers. IgG in sera from immunized mice bound to pneumococcal strains from different serotypes and expressing different PspA clades, indicating broad recognition. Mucosal IgG and IgA were also detected. Importantly, immunization with LP/NCMPs induced full protection against strains expressing PspAs from family 1 and 2. Furthermore, CD4+ resident memory T cells were detected in the lungs of the immunized animals that survived the challenge.

TV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studies.

BACKGROUNDDisease due to dengue viruses is a growing global health threat, causing 100-400 million cases annually. An ideal dengue vaccine should demonstrate durable protection against all 4 serotypes in phase III efficacy trials, however the lack of circulating serotypes may lead to incomplete efficacy data. Controlled human infection models help downselect vaccine candidates and supply critical data to supplement efficacy trials. We evaluated the efficacy of a leading live-attenuated tetravalent dengue vaccine candidate, TV005, against infection with a newly established dengue serotype 3 or an established serotype 2 challenge virus.METHODSTwo randomized, controlled clinical trials were performed. In study 1, a total of 42 participants received TV005 or placebo (n = 21 each), and 6 months later, all were challenged with dengue 2 virus (rDEN2Δ30) at a dose of 103 PFU. In study 2, a total of 23 participants received TV005 and 20 received placebo, and 6 months later, all were challenged with 104 PFU dengue 3 virus (rDEN3Δ30). The study participants were closely monitored for safety, viremia, and immunologic responses. Infection, measured by post-challenge viremia, and the occurrence of rash and neutropenia were the primary endpoints. Secondary endpoints included safety, immunologic, and virologic profiles following vaccination with TV005 and subsequent challenge with the rDEN2Δ30 or rDEN3Δ30 strain.RESULTSTV005 was well tolerated and protected all vaccinated volunteers from viremia with DENV2 or DENV3 (none infected in either group). Placebo recipients had post-challenge viremia (100% in study 1, 85% in study 2), and all experienced rash following challenge with either serotype.CONCLUSIONSTV005 is a leading tetravalent dengue vaccine candidate that fully protected against infection with DENV2 and DENV3 in an established controlled human infection model.TRIAL REGISTRATIONClinicalTrials.gov NCT02317900 and NCT02873260.FUNDINGIntramural Research Program, NIH (contract HHSN272200900010C).

An engineered Accum-E7 protein-based vaccine with dual anti-cervical cancer activity.

Worldwide prevalence of cervical cancer decreased significantly with the use of human papilloma virus (HPV)-targeted prophylactic vaccines. However, these multivalent antiviral vaccines are inert against established tumors, which leave patients with surgical ablative options possibly resulting in long-term reproductive complications and morbidity. In an attempt to bypass this unmet medical need, we designed a new E7 protein-based vaccine formulation using Accum™, a technology platform designed to promote endosome-to-cytosol escape as a means to enhance protein accumulation in target cells. Prophylactic vaccination of immunocompetent mice using the Accum-E7 vaccine (aE7) leads to complete protection from cervical cancer despite multiple challenges conducted with ascending C3.43 cellular doses (0.5-, 1.0-, and 2.0 × 106 cells). Moreover, the humoral response induced by aE7 was higher in magnitude compared with naked E7 protein vaccination and displayed potent inhibitory effects on C3.43 proliferation invitro. When administered therapeutically to animals with pre-established C3.43 or Tal3 tumors, the vaccine-induced response synergized with multiple immune checkpoint blockers (anti-PD-1, anti-CTLA4, and anti-CD47) to effectively control tumor growth. Mechanistically, the observed therapeutic effect requires cross-presenting dendritic cells as well as CD8 T cells predominantly, with a non-negligible role played by both CD4+ and CD19+ lymphocytes. good laboratory practice (GLP) studies revealed that aE7 is immunogenic and well tolerated by immunocompetent mice with no observed adverse effects despite the use of a fourfold exceeding dose. In a nutshell, aE7 represents an ideal vaccine candidate for further clinical development as it uses a single engineered protein capable of exhibiting both prophylactic and therapeutic activity.

A Comprehensive View on the Protein Functions of Porcine Epidemic Diarrhea Virus.

Porcine epidemic diarrhea (PED) virus (PEDV) is one of the main pathogens causing diarrhea in piglets and fattening pigs. The clinical signs of PED are vomiting, acute diarrhea, dehydration, and mortality resulting in significant economic losses and becoming a major challenge in the pig industry. PEDV possesses various crucial structural and functional proteins, which play important roles in viral structure, infection, replication, assembly, and release, as well as in escaping host innate immunity. Over the past few years, there has been progress in the study of PEDV pathogenesis, revealing the crucial role of the interaction between PEDV viral proteins and host cytokines in PEDV infection. At present, the main control measure against PEDV is vaccine immunization of sows, but the protective effect for emerging virus strains is still insufficient, and there is no ideal safe and efficient vaccine. Although scientists have persistently delved their research into the intricate structure and functionalities of the PEDV genome and viral proteins for years, the pathogenic mechanism of PEDV remains incompletely elucidated. Here, we focus on reviewing the research progress of PEDV structural and nonstructural proteins to facilitate the understanding of biological processes such as PEDV infection and pathogenesis.

Development of Vaccines against Emerging Mosquito-Vectored Arbovirus Infections.

Among emergent climate-sensitive infectious diseases, some mosquito-vectored arbovirus infections have epidemiological, social, and economic effects. Dengue virus (DENV), West Nile virus (WNV), and Chikungunya virus (CHIKV) disease, previously common only in the tropics, currently pose a major risk to global health and are expected to expand dramatically in the near future if adequate containment measures are not implemented. The lack of safe and effective vaccines is critical as it seems likely that emerging mosquito-vectored arbovirus infections will be con-trolled only when effective and safe vaccines against each of these infections become available. This paper discusses the clinical characteristics of DENV, WNV, and CHIKV infections and the state of development of vaccines against these viruses. An ideal vaccine should be able to evoke with a single administration a prompt activation of B and T cells, adequate concentrations of protecting/neutralizing antibodies, and the creation of a strong immune memory capable of triggering an effective secondary antibody response after new infection with a wild-type and/or mutated infectious agent. Moreover, the vaccine should be well tolerated, safe, easily administrated, cost-effective, and widely available throughout the world. However, the development of vaccines against emerging mosquito-vectored arbovirus diseases is far from being satisfactory, and it seems likely that it will take many years before effective and safe vaccines for all these infections are made available worldwide.

Nanoparticle-Conjugated Toll-Like Receptor 9 Agonists Improve the Potency, Durability, and Breadth of COVID-19 Vaccines.

Development of effective vaccines for infectious diseases has been one of the most successful global health interventions in history. Though, while ideal subunit vaccines strongly rely on antigen and adjuvant(s) selection, the mode and time scale of exposure to the immune system has often been overlooked. Unfortunately, poor control over the delivery of many adjuvants, which play a key role in enhancing the quality and potency of immune responses, can limit their efficacy and cause off-target toxicities. There is a critical need for improved adjuvant delivery technologies to enhance their efficacy and boost vaccine performance. Nanoparticles have been shown to be ideal carriers for improving antigen delivery due to their shape and size, which mimic viral structures but have been generally less explored for adjuvant delivery. Here, we describe the design of self-assembled poly(ethylene glycol)-b-poly(lactic acid) nanoparticles decorated with CpG, a potent TLR9 agonist, to increase adjuvanticity in COVID-19 vaccines. By controlling the surface density of CpG, we show that intermediate valency is a key factor for TLR9 activation of immune cells. When delivered with the SARS-CoV-2 spike protein, CpG nanoparticle (CpG-NP) adjuvant greatly improves the magnitude and duration of antibody responses when compared to soluble CpG, and results in overall greater breadth of immunity against variants of concern. Moreover, encapsulation of CpG-NP into injectable polymeric-nanoparticle (PNP) hydrogels enhances the spatiotemporal control over codelivery of CpG-NP adjuvant and spike protein antigen such that a single immunization of hydrogel-based vaccines generates humoral responses comparable to those of a typical prime-boost regimen of soluble vaccines. These delivery technologies can potentially reduce the costs and burden of clinical vaccination, both of which are key elements in fighting a pandemic.