Vaccine Formulations Research Articles

Components, Formulations, Deliveries, and Combinations of Tumor Vaccines.

Tumor vaccines, an important part of immunotherapy, prevent cancer or kill existing tumor cells by activating or restoring the body's own immune system. Currently, various formulations of tumor vaccines have been developed, including cell vaccines, tumor cell membrane vaccines, tumor DNA vaccines, tumor mRNA vaccines, tumor polypeptide vaccines, virus-vectored tumor vaccines, and tumor-in-situ vaccines. There are also multiple delivery systems for tumor vaccines, such as liposomes, cell membrane vesicles, viruses, exosomes, and emulsions. In addition, to decrease the risk of tumor immune escape and immune tolerance that may exist with a single tumor vaccine, combination therapy of tumor vaccines with radiotherapy, chemotherapy, immune checkpoint inhibitors, cytokines, CAR-T therapy, or photoimmunotherapy is an effective strategy. Given the critical role of tumor vaccines in immunotherapy, here, we look back to the history of tumor vaccines, and we discuss the antigens, adjuvants, formulations, delivery systems, mechanisms, combination therapy, and future directions of tumor vaccines.

Protection against experimental cryptococcosis elicited by Cationic Adjuvant Formulation 01-adjuvanted subunit vaccines.

The fungal infection, cryptococcosis, is responsible for >100,000 deaths annually. No licensed vaccines are available. We explored the efficacy and immune responses of subunit cryptococcal vaccines adjuvanted with Cationic Adjuvant Formulation 01 (CAF01). CAF01 promotes humoral and T helper (Th) 1 and Th17 immune responses and has been safely used in human vaccine trials. Four subcutaneous vaccines, each containing single recombinant Cryptococcus neoformans protein antigens, partially protected mice from experimental cryptococcosis. Protection increased, up to 100%, in mice that received bivalent and quadrivalent vaccine formulations. Vaccinated mice that received a pulmonary challenge with C. neoformans had an influx of leukocytes into the lung including robust numbers of polyfunctional CD4+ T cells which produced interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), and interleukin (IL)-17 upon ex vivo antigenic stimulation. Cytokine-producing lung CD8+ T cells were also found, albeit in lesser numbers. A significant, durable IFNγ response was observed in the lungs, spleen, and blood. Moreover, IFNγ secretion following ex vivo stimulation directly correlated with fungal control in the lungs. Thus, we have developed multivalent cryptococcal vaccines which protect mice from experimental cryptococcosis using an adjuvant which has been safely tested in humans. These preclinical studies suggest a path towards human cryptococcal vaccine trials.

An optically responsive cancer vaccine for inducing robust anti-tumor immunity by apoptotic body carrying nanoadjuvants

A cancer vaccine based on nano-adjuvant fusion represents an effective strategy for anti-tumor immunity. Compared with other cancer vaccine formulations, the ones based on apoptotic bodies not only possess higher load-bearing capacity and biosafety, but also present greater clinical translational potential. In this study, we developed an optically responsive cancer vaccine that induced robust anti-tumor immunity by encapsulating genipin-crosslinked nano-adjuvants in tumor cell apoptotic bodies. The vaccine may potentially be used for prophylactic or therapeutic purposes. As an antigen source and a cargo vehicle, apoptotic bodies can co-deliver antigens and adjuvants simultaneously to antigen-presenting cells to activate T cells. Nano-adjuvants promote the targeted delivery of adjuvants for effective immune responses. Genipin-crosslinked nano-adjuvants enable visual tracking of the tumor vaccine. In addition, the photothermal properties of genipin-crosslinked nano-adjuvants promote lysosomal escape of tumor antigens to enhance cross-presentation. These characteristics enable visualization and controllability of cancer vaccines, thereby avoiding the need for exogenous photosensitive reagents. Apoptotic body-based vaccines can be used to prevent or treat tumors by triggering a strong systemic immune response by promoting T-cell infiltration and improving the tumor immune microenvironment.

Influence of bovine pestivirus heterogeneity on serological responses to 10 different commercial vaccine formulation

Bovine Pestivirus typically involves one or more organ systems, with clinical manifestations ranging from mild to severe fatal systemic illness that lead to significant reproductive, productive, and economic losses. Vaccines face the challenge of addressing the significant variability of pestiviruses, which affects the interaction between viral antigens and the immune system’s ability to provide protection. This study aimed to evaluate the serological responses against bovine viral diarrhea virus 1 (Pestivirus A) and Pestivirus B induced by 10 commercial vaccines, including one recombinant (vaccine E), two modified live (MLV multivalent, vaccine I, and MLV monovalent, vaccine J), and seven killed vaccines (KLV, vaccines A to H). Additionally, we evaluated the cross-reactivity between Pestivirus A and B from vaccines and HoBi-like pestivirus (Pestivirus H). In Phase 1, guinea pigs were used to screen for non-MLVs. They were divided into nine groups (n=6 each) and received two doses (⅕ of bovine dose) of eight different non-MLV on Days 0 and 21. Serum samples were collected on Days 0 and 30 for serological analyse. In Phase 2, Holstein × Gir heifers (n= 45) were divided into five groups, comprising 6–9 animals. They were vaccinated either once with MLVs or twice with the top non-MLVs screened in Phase 1. Serum samples were harvested on d0 (vaccination day) and d60 (60 days after the first dose) for MLV and non-MLV. Specific antibody titers were assessed virus neutralization (VN) and transformed in log2 for statistical analysis using PROC-MIXED. Significant effects were observed for vaccine groups, time points, and their interactions concerning neutralizing antibodies against Pestivirus A and B in both Guinea pigs and heifers. The Phase 1 study revealed serological responses against Pestivirus A exclusively in non-MLV D (85.33±13.49) and E (72.00±19.26). In the bovine study, the KLD vaccine D (72.00±15.10), recombinant vaccine E (90.66±25.85), and MLV I (170.66±28.22) resulted in an average of neutralizing antibodies against Pestivirus A that exceeded the protective threshold (≥ 60). However,individual analysis of heifers showed a higher frequency of animals presenting titers of Pestivirus A Ab surpassing 32 following vaccination with MLV I and J. None of the vaccine formulations in either study elicited a protective immune response against Pestivirus B or demonstrated cross-reactivity against Pestivirus H.

An Immunoreceptor-Targeting Strategy with Minimalistic C3b Peptide Fusion Enhances SARS-CoV-2 RBD mRNA Vaccine Immunogenicity.

The clinical success of mRNA vaccine during the COVID-19 pandemic has inspired emerging approaches to elevate mRNA vaccine immunogenicity. Among them, antigen fusion protein designs for improved immune cell targeting have been shown to augment humoral immunity against small antigen targets. This research demonstrates that SARS-CoV-2 receptor binding domain (RBD) fusion with a minimalistic peptide segment of complement component 3b (C3b, residues 727-767) ligand can improve mRNA vaccine immunogenicity through antigen targeting to complement receptor 1 (CR1). We affirm vaccines' antigenicity and targeting ability towards specific receptors through Western blot and immunofluorescence assay. Furthermore, mice immunization studies help the investigation of the antibody responses. Using SARS-CoV-2 Omicron RBD antigen, we compare mRNA vaccine formulations expressing RBD fusion protein with mouse C3b peptide (RBD-mC3), RBD fusion protein with mouse Fc (RBD-Fc), and wild-type RBD. Our results confirm the proper antigenicity and normal functionality of RBD-mC3. Upon validating comparable antigen expression by the different vaccine formulations, receptor-targeting capability of the fusion antigens is further confirmed. In mouse immunization studies, we show that while both RBD-mC3 and RBD-Fc elevate vaccine immunogenicity, RBD-mC3 leads to more sustained RBD-specific titers over the RBD-Fc design, presumably due to reduced antigenic diversion by the minimalistic targeting ligand. The study demonstrates a novel C3b-based antigen design strategy for immune cell targeting and mRNA vaccine enhancement.

Identification of linear B cell epitopes on the leukotoxin protein of Fusobacterium necrophorum

ObjectiveFusobacterium necrophorum can casuse Lemierre's syndrome in humans and a range of illnesses, including foot rot and liver abscesses, in animals. The main virulence factor released by F. necrophorum is leukotoxin, which has been shown to have a strong correlation with the severity of the disease. Leukotoxin is commonly employed as the key antigen in the formulation of subunit vaccines. Therefore, identification of the B-cell epitope of F. necrophorum leukotoxin is necessary. MethodsIn this research, we utilized lymphocyte hybridoma technology to develop a monoclonal antibody (mAb), 3D7, targeting the F. necrophorum leukotoxin protein. Identification of B-cell epitopes recognized by 3D7 mAb was achieved through Western blot, ELISA and dot blots using leukotoxin-truncated recombinant proteins and peptides, and through SWISS-MODEL homology modeling and PyMOL visualization. ResultsThe 3D7 mAb was identified as belonging to the IgG1 subclass with a κ-chain light chain. It demonstrated reactivity with the natural leukotoxin. The results showed that the 3D7 mAb recognizes a B-cell epitope of the F. necrophorum leukotoxin protein, I2168SSFGVGV2175 (EP-3D7). Sequence comparison analysis showed that EP-3D7 was highly conserved in F. necrophorum strains, but less conserved in other bacteria, indicating the specificity of EP-3D7. EP-3D7 is present on the surface of leukotoxin proteins in a β-folded manner. ConclusionsIn summary, these results establish EP-3D7 as a conserved antigenic epitope of F. necrophorum leukotoxin. It could be valuable in the development of vaccines and diagnostic reagents for F. necrophorum epitopes.

SARS-CoV-2 Molecular Evolution: A Focus on Omicron Variants in Umbria, Italy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 6 million deaths worldwide, and the spread of new variants over time increased the ability of this virus to cause infection. The Omicron variant was detected for the first time in Umbria, a region of central Italy, in November 2021 and it induced an unprecedented increase in the number of infection cases. Here, we analysed 3300 SARS-CoV-2 positive samples collected in Umbria between April 2022 and December 2023. We traced the molecular evolution of SARS-CoV-2 variants over time through the Next-Generation Sequencing (NGS) approach. We assessed correlation between SARS-CoV-2 infection and patients' health status. In total, 17.3% of our samples came from patients hospitalised as a consequence of COVID-19 infection even though 81.4% of them received at least three vaccine doses. We identified only Omicron variants, and the BA.5 lineage was detected in the majority of our samples (49.2%). Omicron variants outcompeted each other through the acquisition of mutations especially in Spike glycoprotein that are fingerprints of each variant. Viral antigenic evolution confers higher immunological escape and makes a continuous improvement of vaccine formulation necessary. The continuous update of international genomic databases with sequencing results obtained by emergent pathogens is essential to manage a possible future pandemic.

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.

Buccal Administration of a Zika Virus Vaccine Utilizing 3D-Printed Oral Dissolving Films in a Mouse Model.

Over the years, research regarding the Zika virus has been steadily increasing. Early immunization for ZIKV is a priority for preventing complications such as microencephaly and Guillain-Barré syndrome (GBS). Unlike traditional vaccination approaches, oral dissolving films (ODFs) or mucoadhesive film technology is an emerging, exciting concept that can be used in the field of pharmaceuticals for vaccine design and formulation development. This attractive and novel method can help patients who suffer from dysphagia as a complication of a disease or syndrome. In this study, we investigated a microparticulate Zika vaccine administered via the buccal route with the help of thin films or oral dissolving films (ODFs) with a prime dose and two booster doses two weeks apart. In vitro, the ODFs displayed excellent physiochemical properties, indicating that the films were good carriers for vaccine microparticles and biocompatible with the buccal mucosa. In vivo results revealed robust humoral (IgG, subtypes IgG1 and IgG2a) and T-cell responses (CD4+/CD8+) for ZIKV-specific immunity. Both the Zika MP vaccine and the adjuvanted Zika MP vaccine affected memory (CD45R/CD27) and intracellular cytokine (TNF-α and IL-6) expression. In this study, ZIKV vaccination via the buccal route with the aid of ODFs demonstrated great promise for the development of pain-free vaccines for infectious diseases.

Polymyalgia Rheumatica Following Respiratory Syncytial Virus (RSV) Vaccination.

Polymyalgia rheumatica (PMR) is a chronic inflammatory disorder that causes stiffness and pain in the proximal joints, including the shoulders, hips and neck. The exact cause of polymyalgia rheumatica is yet to be fully understood, but research suggests that both genetic and environmental factors may contribute to it. Studies have previously linked the onset and relapse of polymyalgia rheumatica symptoms to the influenza and COVID-19 vaccines. The Food and Drug Administration approved the respiratory syncytial virus (RSV) vaccine, which is a recombinant protein vaccine for adults over 60, in May 2023. No previous reports of polymyalgia rheumatica onset or relapse have been linked to the RSV vaccine. The human proteome shares some peptides with the RSV F antigen, suggesting a high risk of cross-reactivity when using that antigen in vaccination formulations. A 72-year-old man experienced a new onset of bilateral shoulder pain and stiffness three days after receiving the Abrysvo® RSV vaccine. The symptoms lasted more than an hour (up until noon) and interfered with his activities of daily living. Inflammatory markers such as C-reactive protein were elevated. The patient's symptoms and inflammatory marker levels significantly improved with prednisone therapy. In patients with typical PMR symptoms, it is important for clinicians to carefully review immunisation history to rule out any potentially related adverse effects. Vaccines can trigger autoimmune diseases in some individuals.This case report suggests respiratory syncytial virus (RSV) vaccine is among the possible triggers for polymyalgia rheumatica.

Aluminum oxyhydroxide-Poly(I:C) combination adjuvant with balanced immunostimulatory potentials for prophylactic vaccines

The development of high-purity antigens promotes the urgent need of novel adjuvant with the capability to trigger high levels of immune response. Polyinosinic-polycytidylic (Poly(I:C)) is a synthetic double-stranded RNA (dsRNA) that can engage Toll-like receptor 3 (TLR3) to initiate immune responses. However, the Poly(I:C)-induced toxicity and inefficient delivery prevent its applications. In our study, combination adjuvants are formulated by aluminum oxyhydroxide nanorods (AlOOH NRs) and Poly(I:C), named Al-Poly(I:C), and the covalent interaction between the two components is further demonstrated. Al-Poly(I:C) mediates enhanced humoral and cellular immune responses in three antigen models, i.e., HBsAg virus-like particles (VLPs), human papilloma virus (HPV) VLPs and varicella-zoster virus (VZV) glycoprotein E (gE). Further mechanistic studies demonstrate that the dose and molecular weight (MW) of Poly(I:C) determine the physicochemical properties and adjuvanticity of the Al-Poly(I:C) combination adjuvants. Al-Poly(I:C) with higher Poly(I:C) dose promotes antigen-bearing dendritic cells (DCs) recruitment and B cells proliferation in lymph nodes. Al-Poly(I:C) formulated with higher MW Poly(I:C) induces higher activation of helper T cells, B cells, and CTLs. This study demonstrates that Al-Poly(I:C) potentiates the humoral and cellular responses in vaccine formulations. It offers insights for adjuvant design to meet the formulation requirements in both prophylactic and therapeutic vaccines.

PH-Responsive β-Glucans-Complexed mRNA in LNPs as an Oral Vaccine for Enhancing Cancer Immunotherapy.

mRNA vaccines for cancer immunotherapy are commonly delivered using lipid nanoparticles (LNPs), which, when administered intravenously, may accumulate in the liver, potentially limiting their therapeutic efficacy. To overcome this challenge, the study introduces an oral mRNA vaccine formulation tailored for efficient uptake by immune cells in the gastrointestinal (GI) tract, known for its high concentration of immune cells, including dendritic cells (DCs). This formulation comprises mRNA complexed with β-glucans (βGlus), a potential adjuvant for vaccines, encapsulated within LNPs (βGlus/mRNA@LNPs). The βGlus/mRNA complexes within the small compartments of LNPs demonstrate a distinctive ability to partially dissociate and reassociate, responding to pH changes, effectively shielding mRNA from degradation in the harsh GI environment. Upon oral administration to tumor-bearing mice, βGlus/mRNA@LNPs are effectively taken up by intestinal DCs and local nonimmune cells, bypassing potential liver accumulation. This initiates antigen-specific immune responses through successful mRNA translation, followed by drainage into the mesenteric lymph nodes to stimulate T cells and trigger specific adaptive immune responses, ultimately enhancing antitumor effects. Importantly, the vaccine demonstrates safety, with no significant inflammatory reactions observed. In conclusion, the potential of oral βGlus/mRNA@LNPs delivery presents a promising avenue in cancer immunotherapy, offering needle-free and user-friendly administration for widespread adoption and self-administration.

Construction and immunogenicity of SARS-CoV-2 virus-like particle expressed by recombinant baculovirus BacMam.

Although existing vaccines have significantly mitigated the impact of the COVID-19 pandemic, none of the vaccines can induce sterilizing immunity. The spike protein is the main component of all approved vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due primarily to its ability to induce neutralizing antibodies. The conformation of the spike protein in the vaccine formulation should be critical for the efficacy of a vaccine. By way of closely resembling the authentic virions, virus-like particles (VLPs) should render the spike protein in its natural conformation. To this end, we utilized the baculovirus vector, BacMam, to express virus-like particles consisting of the spike, membrane, and envelope proteins of SARS-CoV-2. We demonstrated the immunogenicity of our VLP vaccine with neutralizing activity. Our data warrant further evaluation of the virus-like particles as a vaccine candidate in protecting against virus challenges.

Assessing population-level target product profiles of universal human influenza A vaccines

Influenza A has two hemagglutinin groups, with stronger cross-immunity to reinfection within than between groups. Here, we explore the implications of this heterogeneity for proposed cross-protective influenza vaccines that may offer broad, but not universal, protection. While the development goal for the breadth of human influenza A vaccine is to provide cross-group protection, vaccines in current development stages may provide better protection against target groups than non-target groups. To evaluate vaccine formulation and strategies, we propose a novel perspective: a vaccine population-level target product profile (PTPP). Under this perspective, we use dynamical models to quantify the epidemiological impacts of future influenza A vaccines as a function of their properties. Our results show that the interplay of natural and vaccine-induced immunity could strongly affect seasonal subtype dynamics. A broadly protective bivalent vaccine could lower the incidence of both groups and achieve elimination with sufficient vaccination coverage. However, a univalent vaccine at low vaccination rates could permit a resurgence of the non-target group when the vaccine provides weaker immunity than natural infection. Moreover, as a proxy for pandemic simulation, we analyze the invasion of a variant that evades natural immunity. We find that a future vaccine providing sufficiently broad and long-lived cross-group protection at a sufficiently high vaccination rate, could prevent pandemic emergence and lower the pandemic burden. This study highlights that as well as effectiveness, breadth and duration should be considered in epidemiologically informed TPPs for future human influenza A vaccines.

A Computationally Optimized Broadly Reactive Hemagglutinin and Neuraminidase Vaccine Boosts Antibody-Secreting Cells and Induces a Robust Serological Response, Preventing Lung Damage in a Pre-Immune Model.

The hemagglutinin (HA) and neuraminidase (NA) surface proteins are the primary and secondary immune targets for most influenza vaccines. In this study, H2, H5, H7, N1, and N2 antigens designed by the computationally optimized broadly reactive antigen (COBRA) methodology were incorporated into an adjuvant-formulated vaccine to assess the protective efficacy and immune response against A/Hong Kong/125/2017 H7N9 virus challenge in pre-immune mice. The elicited antibodies bound to H2, H5, H7, N1, and N2 wild-type antigens; cH6/1 antigens; and cH7/3 antigens, with hemagglutinin inhibition (HAI) activity against broad panels of the H2Nx, H5Nx, and H7Nx influenza strains. Mice vaccinated with the pentavalent COBRA HA/NA vaccine showed little to no weight loss, no clinical signs of diseases, and were protected from mortality when challenged with the lethal H7N9 virus. Virus titers in the lungs of vaccinated mice were lower and cleared more rapidly than in mock-vaccinated mice. Some vaccinated mice showed no detectable lung injury or inflammation. Antibody-secreting cells were significantly increased in COBRA-vaccinated mice, with higher total Ig and H7-specific ASC. Thus, the combination of H2, H5, H7, N1, and N2 COBRA antigens presents a potential for the formulation of a universal influenza virus vaccine.

Flagellin Enhances the Immunogenicity of Pasteurella multocida Lipoprotein E Subunit Vaccine.

Fowl cholera, caused by Pasteurella multocida infection, poses challenges for prevention because of its many serotypes. Bacterins are currently widely used for vaccination against fowl cholera, but protection is limited to homologous strains. Live attenuated vaccines of P. multocida provide some heterologous protection, but side effects are considerable. More recently, protein-based antigens are promising subunit vaccines when their low immunogenicity has been addressed with effective adjuvants. Bacterial flagellin has been widely considered a promising adjuvant for vaccines. In this study, we tested the adjutancy of flagellin in a subunit vaccine against P. multocida in a mice and chicken models. For vaccine formulation, the antigen fPlpE (P. multocida liporotein E) was combined with fFliC (Salmonella Typhimurium flagellin). The recombinant proteins of fPlpE and fFliC were successfully expressed using the Escherichia coli system as the expected sizes of 55 kDa and 70 kDa, respectively. The fFliC elicited strong expression levels of proinflammatory cytokine (IL-1β, IL-8, and IL-6) when stimulated in native chicken peripheral blood mononuclear cells. Immunization of mice and chickens with the subunit vaccines containing fFliC accelerated the antibody response. In the challenge tests, fFliC increased vaccine protective efficacy against the heterologous strain P. multocida A1 and highly virulent strain Chu01 in mice and chickens, respectively. These data indicated potential possibilities of using fFliC as an immunostimulant adjuvant in developing a subunit vaccine against fowl cholera.

Immunogenicity of PvCyRPA, PvCelTOS and Pvs25 chimeric recombinant protein of Plasmodium vivax in murine model.

In the Americas, P. vivax is the predominant causative species of malaria, a debilitating and economically significant disease. Due to the complexity of the malaria parasite life cycle, a vaccine formulation with multiple antigens expressed in various parasite stages may represent an effective approach. Based on this, we previously designed and constructed a chimeric recombinant protein, PvRMC-1, composed by PvCyRPA, PvCelTOS, and Pvs25 epitopes. This chimeric protein was strongly recognized by naturally acquired antibodies from exposed population in the Brazilian Amazon. However, there was no investigation about the induced immune response of PvRMC-1. Therefore, in this work, we evaluated the immunogenicity of this chimeric antigen formulated in three distinct adjuvants: Stimune, AddaVax or Aluminum hydroxide (Al(OH)3) in BALB/c mice. Our results suggested that the chimeric protein PvRMC-1 were capable to generate humoral and cellular responses across all three formulations. Antibodies recognized full-length PvRMC-1 and linear B-cell epitopes from PvCyRPA, PvCelTOS, and Pvs25 individually. Moreover, mice's splenocytes were activated, producing IFN-γ in response to PvCelTOS and PvCyRPA peptide epitopes, affirming T-cell epitopes in the antigen. While aluminum hydroxide showed notable cellular response, Stimune and Addavax induced a more comprehensive immune response, encompassing both cellular and humoral components. Thus, our findings indicate that PvRMC-1 would be a promising multistage vaccine candidate that could advance to further preclinical studies.

An Overview of the Strategies to Boost SARS-CoV-2-Specific Immunity in People with Inborn Errors of Immunity.

The SARS-CoV-2 pandemic has heightened concerns about immunological protection, especially for individuals with inborn errors of immunity (IEI). While COVID-19 vaccines elicit strong immune responses in healthy individuals, their effectiveness in IEI patients remains unclear, particularly against new viral variants and vaccine formulations. This uncertainty has led to anxiety, prolonged self-isolation, and repeated vaccinations with uncertain benefits among IEI patients. Despite some level of immune response from vaccination, the definition of protective immunity in IEI individuals is still unknown. Given their susceptibility to severe COVID-19, strategies such as immunoglobulin replacement therapy (IgRT) and monoclonal antibodies have been employed to provide passive immunity, and protection against both current and emerging variants. This review examines the efficacy of COVID-19 vaccines and antibody-based therapies in IEI patients, their capacity to recognize viral variants, and the necessary advances required for the ongoing protection of people with IEIs.

Immunological effects of DNA vaccination and interleukin utilization as an adjuvant in Astyanax lacustris immunized against Ichthyophthirius multifiliis.

The increasing significance of the aquaculture sector and commercially valuable species underscores the need to develop alternatives for controlling diseases such as Ichthyophthirius multifiliis-induced ichthyophthiriasis. This ciliated protozoan parasite threatensnearly all freshwater fish species, causing substantial losses in the fishery industry. Despite this, effective large-scale treatments are lacking, emphasizing the necessity of adopting preventive strategies. While the pathogenesis of ichthyophthiriasis and its immune stimulation allows for vaccination strategies, precise adjustments are crucial to ensure the production of an effective vaccine compound. Therefore, this study aimed to evaluate the impact of immunizing Astyanax lacustris with a genetic vaccine containing IAG52A from I. multifiliis and the molecular adjuvant IL-8 from A. lacustris. Transcript analysis in immunized A. lacustris indicated mRNA production in fish muscles, demonstrating an expression of this mRNA. Fish were divided into five groups, receiving different vaccine formulations, and all groups received a booster dose 14 days after the initial immunization. Samples from vaccinated fish showed increased IL-1β mRNA expression in the spleen within 6 h post the second dose and after 14 days. In the head kidney, IL-1β mRNA expression showed no significant difference at 6 and 24 h but an increase was noted in fish injected with IAG and IAG + IL-8 after 14 days. IL-8 mRNA expression in the spleen and kidney did not significantly differ from the control group. Histological analysis revealed no variation in leukocyte concentration at 6 and 24 h post-vaccination; however, after 14 days, the groups injected with IAG and IAG + IL-8 exhibited a higher leukocyte density at the application sites thanthe control. The obtained data suggest that the used vaccine is transcribed, indicating its potential to stimulate innate immune response parameters through mRNA cytokine expression and leukocyte migration.

1065-P: Comparative Effectiveness of the Bivalent COVID-19 mRNA Vaccines mRNA1273-222 and BNT162b2 in Adults with Diabetes in the U.S.

Introduction & Objective: Diabetes is associated with an increased risk for severe COVID-19. A subanalysis of a retrospective observational cohort study was conducted to evaluate the relative vaccine effectiveness (rVE) of 2 previously approved bivalent vaccines that target the ancestral SARS-CoV-2 and the omicron BA.4/BA.5 variant, mRNA-1273.222 (Moderna, Inc.) and BNT162b2 bivalent (Pfizer-BioNTech), in US adults with diabetes. Methods: The study used a US electronic health record dataset (Veradigm) linked with medical claims data of adults aged ≥18 years with ≥1 underlying medical condition associated with increased risk of severe COVID-19 who received a dose of mRNA-1273.222 or BNT162b2 bivalent vaccines between August 31, 2022, and February 28, 2023. The current analysis included a subgroup of individuals with type 1 or type 2 diabetes identified in the dataset by ICD-10 diagnostic code. The rVE was measured against COVID-19-related hospitalizations and COVID-19-related outpatient visits. Follow-up started 7 days after vaccination until May 31, 2023. Propensity score weighting was used to adjust for baseline differences between groups. Results: Of 639,868 individuals with diabetes included in the analysis, 252,635 received mRNA-1273.222, and 387,233 received BNT162b2 bivalent (post-weighting). After weighting, no variables had an SMD >0.1 therefore no adjustments were made to rVE estimates. The adjusted rVEs of mRNA-1273.222 versus BNT162b2 bivalent vaccine against COVID-19-related hospitalizations and outpatient visits were 15.1% (95% CI, 8.7%-21.0%) and 3.7% (95% CI, 1.2%-6.2%), respectively. Conclusion: We found greater effectiveness of mRNA-1273.222 compared with the BNT162b2 bivalent vaccine in preventing COVID-19—related hospitalizations in this cohort of individuals with diabetes. This study emphasizes the importance of assessing COVID-19 vaccine formulations in high-risk adults, including those with diabetes. Disclosure H. Kopel: Employee; Moderna, Inc. Stock/Shareholder; Moderna, Inc. V. Nguyen: Employee; VHN Consulting Inc. Other Relationship; Moderna, Inc. A. Bogdanov: Employee; Veradigm. Other Relationship; Moderna, Inc. I. Winer: Employee; Veradigm. Other Relationship; Moderna, Inc. C. Boileau: Employee; VHN Consulting Inc. Other Relationship; Moderna, Inc. T. Ducruet: Employee; VHN Consulting Inc. Other Relationship; Moderna, Inc. N. Zeng: Employee; Veradigm. Other Relationship; Moderna, Inc. M. Bausch-Jurken: Employee; Moderna, Inc. Stock/Shareholder; Moderna, Inc. D.B. Esposito: Employee; Moderna, Inc. Stock/Shareholder; Moderna, Inc. E. Beck: Employee; Moderna, Inc. Stock/Shareholder; Moderna, Inc. M. Bonafede: Employee; Veradigm. Other Relationship; Moderna, Inc. J.A. Mansi: Employee; Moderna, Inc. Stock/Shareholder; Moderna, Inc.