Different Platforms, Immune Response Modulators and Challenges in SARS-CoV- 2 Vaccination

Vaccination is one of the most powerful measures to control infectious diseases. Nowadays, technical advances allowed the recognition of key aspects of pathogen -host interaction and the spread of such information, which was applied in vaccine development. The urge to control the COVID-19 pandemic resulted in vaccines development in record time, approximately 1 year after the emergence of SARS-CoV-2. The use of classic and innovative vaccine platforms and adjuvants was employed at several locations, by different groups. Here, we discuss how the pandemic scenario influences vaccine development, the implications of the route of immunization and adjuvant choice for vaccines, and the need to consider all these aspects in relation to the current scenario, also preparing ourselves to future pandemics. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

PROGNOSTIC FACTORS AND EFFICACY OF DMARD USE IN GCA: RESULTS FROM THE PROSPECTIVE, LONGITUDINAL,MULTI-CENTRE HAS-GCA STUDY

BackgroundGCA is a critically ischemic large vessel vasculitis, varying in extent, severity and outcomes, hence requires disease stratification using clinical, laboratory and imaging parameters, for targeted management. Although DMARDs are used, the effectiveness in real life, such adjuvants remain un-elucidated. We performed a prospective, multi centre cohort study of new GCA stratified into remitting, relapsing, refractory, ischemic disease.ObjectivesWe assessed prognostic factors and compared critical outcomes such as remission with glucocorticoid (GC) monotherapy versus GC plus DMARDs in the first 12 months.MethodsHAS GCA study (1) recruited consecutive patients with new onset GCA from 7 centres (UK, Italy, Spain, Netherlands). diagnosis was confirmed used a modified GiACTA criteria at 6 months follow up. All underwent ultrasound (bilateral common, parietal, frontal temporal arteries, and axillary arteries) using accepted standard cut-off values [2]. GCA patients had US at baseline,1,3,6,12 months and halo count (HC) and Halo score (Temporal TAHS, axillary AAHS, total THS) assessed [3]. The primary outcome- remission at 12 months (absence of signs/symptoms, CRP<5 mg/dl, prednisolone < 5 mg daily). Results are reported as descriptive statistics.Results229 participants included in the study (GCA- 84 (36.68 %) (Figure 1). Study recruited during Covid pandemic,73 completed,11 lost to follow-up (died -7, withdrawn-4). The deceased/withdrawn patients (compared to completers) were older (80 v74 yrs, p=0.018), preponderantly male (73% v 36%, p=0.043) with visual symptoms (91% v 49%, p=0.010) partial/total sight loss (55% v 21%, p=0.024), lower CRP (21 v 68, p=0.061) and ESR (42 v 62, p= 0.317).Of 73 completers 36 required early DMARDs (<12 weeks) for refractory/relapsing/ischemic/GC related AEs. This group had more LV involvement (50% v 11%, p=0.0003), Remission attained at 12 months 32/36 (89%) in DMARD group was comparable to the remitting GC monotherapy group 33/37 (89%) with comparable cumulative GC doses (Figure 1, Table 1).At 12-months follow up, median TAHS, AAHS and THS reduced from 13 to 3, 12 to 9 and 21.5 to 12, respectively.ConclusionOur study suggests, elderly males with visual symptoms, sight loss, lower CRP are a high-risk group with increased mortality within GCA. Difficult to treat disease is seen in half of all patients especially with LV involvement. This group responds well to early DMARD use achieving remission comparable to the remitting group at 12 months. Current therapies fail to achieve remission in 9.5 % of cases. HS and HC show significant improvement mirroring clinical outcomes during first 12 months of therapy.References[1]Sebastian A et al. BMC Rheum. 2020[2]Schafer VS et al. Rheumatology 2017[3]van der Geest KSM et al. ARD 2020Table 1.comparison between the DMARD-used group and only GC group in all the GCA completed the 12 months follow upPatients' characteristicsGCA with completed follow-up (n=73)GCA treated with DMARD=36GCA not treated with DMARD=37Age, median (range) years73.5 (60-89)76 (60-89)Sex, Females, n (%)23 (64)24 (65)US halo score (HS)/IMT median (range)Temporal artery HS11 (0-23)13 (1-22)Axillary artery HS12 (0-21)12 (0-18)Axillary artery IMT (mm)0.77 (0.33-2.6)0.82 (0.39-1.21)Total HS22.5 (2-41)21 (5-40)Clinical features, n (%)Temporal headache25(69)30 (81)Scalp tenderness17 (47)19 (51)Jaw & Tongue claudication22 (61)24 (65)Polymyalgic symptoms21 (58)13 (35)Constitutional symptoms21 (58)18 (49)Any visual disturbance15 (42)21 (57)Partial or complete vision loss8 (22)7 (19)History of PMR6 (17)3 (8)Exam findings, n (%)Temporal artery abnormality24 (67)30 (81)AION/ CRAO8 (22)6 (16)Ocular nerve palsy1 (3)3 (8)Lab markers at baseline, median (range)CRP mg/dL,72.2 (6.4-292)59 (6-206)ESR mm/hr67 (9-130)57 (2-120)GC treatment, median (range)GC starting dose, (baseline)45 (0-60)50 (0-60)GC dose at 12m,5 (0-25)2.5 (0-10)Cumulative GC dose at 12m4627.5 (2600-10260.5)4622.5 (944-10737.5)Remission with prednisolone dose ≤5 mg at 12m, n (%)32 (89)33 (89)Acknowledgements:NIL.Disclosure of InterestsBhaskar Dasgupta Consultant of: Roche, Chugai, Sanofi, Grant/research support from: Roche, Sanofi, AbbVie, and GlaxoSmithKline, Kornelis van der Geest Speakers bureau: Roche, Grant/research support from: AbbVie, Alessandro Tomelleri: None declared, Pierluigi Macchioni: None declared, Giulia Klinowski: None declared, Carlo Salvarani: None declared, Abdul Kayani: None declared, Mohammad Tariq: None declared, Diana Prieto-Peña: None declared, Edoardo Conticini: None declared, Muhammad Khurshid: None declared, Sue Inness: None declared, Jo Jackson: None declared, Alwin Sebastian: None declared.

IgA Vasculitis Following COVID-19 Vaccination.

IgA vasculitis is generally triggered by infectious causes, but it has also been reported after immunization with various vaccines. Herein, we report two cases of IgA vasculitis after receiving the first or second dose of the Pfizer-BioNTech BNT16B2b2 mRNA vaccine. Two men, aged 22 and 30 years, developed palpable purpura on the extremities and arthritis. One patient also complained of fever and gastrointestinal symptoms. Laboratory findings revealed mild leukocytosis and slightly elevated C-reactive protein level, although platelet count and coagulation profile were within normal levels in both cases. Proteinuria and microhematuria were seen in one patient. Skin biopsies were performed in both patients and revealed leukocytoclastic vasculitis. The deposit of IgA and C3 was shown on immunofluorescence studies in one patient. Both patients were diagnosed with IgA vasculitis and treated with prednisolone, and their symptoms resolved within 1 week after initiation of treatment. The COVID-19 mRNA vaccine could trigger IgA vasculitis; however, a coincidence cannot be ruled out.

Adjuvants for COVID-19 Vaccines.

In recent decades, the improvement of traditional vaccines has meant that we have moved from inactivated whole virus vaccines, which provoke a moderate immune response but notable adverse effects, to much more processed vaccines such as protein subunit vaccines, which despite being less immunogenic have better tolerability profiles. This reduction in immunogenicity is detrimental to the prevention of people at risk. For this reason, adjuvants are a good solution to improve the immunogenicity of this type of vaccine, with much better tolerability profiles and a low prevalence of side effects. During the COVID-19 pandemic, vaccination focused on mRNA-type and viral vector vaccines. However, during the years 2022 and 2023, the first protein-based vaccines began to be approved. Adjuvanted vaccines are capable of inducing potent responses, not only humoral but also cellular, in populations whose immune systems are weak or do not respond properly, such as the elderly. Therefore, this type of vaccine should complete the portfolio of existing vaccines, and could help to complete vaccination against COVID-19 worldwide now and over the coming years. In this review we analyze the advantages and disadvantages of adjuvants, as well as their use in current and future vaccines against COVID-19.

The Influence of Adjuvant Type on the Immunogenicity of RBD/N Cocktail Antigens as a Vaccine Candidate against SARS-CoV-2 Virus.

The emerging virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2 virus), agent of COVID-19, appeared in December 2019 in Wuhan, China, and became a serious threat to global health and public safety. Many COVID-19 vaccines have been approved and licensed around the world. Most of the developed vaccines include S protein and induce an antibody-based immune response. Additionally, T-cell response to the SARS-CoV-2 antigens could be beneficial for combating the infection. The type of immune response is greatly dependent not only on the antigen, but also on adjuvants used in vaccine formulation. Here, we compared the effect of four different adjuvants (AddaS03, Alhydrogel/MPLA, Alhydrogel/ODN2395, Quil A) on the immunogenicity of a mixture of recombinant RBD and N SARS-CoV-2 proteins. We have analyzed the antibody and T-cell response specific to RBD and N proteins and assessed the impact of adjuvants on virus neutralization. Our results clearly indicated that Alhydrogel/MPLA and Alhydrogel/ODN2395 adjuvants elicited the higher titers of specific and cross-reactive antibodies to S protein variants from various SARS-CoV-2 and SARS-CoV-1 strains. Moreover, Alhydrogel/ODN2395 stimulated high cellular response to both antigens, as assessed by IFN-γ production. Importantly, sera collected from mice immunized with RBD/N cocktail in combination with these adjuvants exhibited neutralizing activity against the authentic SARS-CoV-2 virus as well as particles pseudotyped with S protein from various virus variants. The results from our study demonstrate the immunogenic potential of RBD and N antigens and point out the importance of adjuvants selection in vaccine formulation in order to enhance the immunological response. IMPORTANCE Although several COVID-19 vaccines have been approved worldwide, continuous emergence of new SARS-CoV-2 variants calls for new efficient vaccines against them, providing long-lasting immunity. As the immune response after vaccination is dependent not only on antigen used, but also on other vaccine components, e.g., adjuvants, the purpose of this work was to study the effect of different adjuvants on the immunogenicity of RBD/N SARS-CoV-2 cocktail proteins. In this work, it has been shown that immunization with both antigens plus the different adjuvants studied elicited higher Th1 and Th2 responses against RBD and N, which contributed to higher neutralization of the virus. The obtained results can be used for design of new vaccines, not only against SARS-CoV-2, but also against other important viral pathogens.

Adenovirus Encoded Adjuvant (AdEnA) anti-CTLA-4, a novel strategy to improve Adenovirus based vaccines against infectious diseases and cancer.

Introduction: Virus vectored genetic vaccines (Vvgv) represent a promising approach for eliciting immune protection against infectious diseases and cancer. However, at variance with classical vaccines to date, no adjuvant has been combined with clinically approved genetic vaccines, possibly due to the detrimental effect of the adjuvant-induced innate response on the expression driven by the genetic vaccine vector. We reasoned that a potential novel approach to develop adjuvants for genetic vaccines would be to "synchronize" in time and space the activity of the adjuvant with that of the vaccine. Methods: To this aim, we generated an Adenovirus vector encoding a murine anti-CTLA-4 monoclonal antibody (Ad-9D9) as a genetic adjuvant for Adenovirus based vaccines. Results: The co-delivery of Ad-9D9 with an Adeno-based COVID-19 vaccine encoding the Spike protein resulted in stronger cellular and humoral immune responses. In contrast, only a modest adjuvant effect was achieved when combining the vaccine with the same anti-CTLA-4 in its proteinaceous form. Importantly, the administration of the adjuvant vector at different sites of the vaccine vector abrogates the immunostimulatory effect. We showed that the adjuvant activity of Ad-α-CTLA-4 is independent from the vaccine antigen as it improved the immune response and efficacy of an Adenovirus based polyepitope vaccine encoding tumor neoantigens. Discussion: Our study demonstrated that the combination of Adenovirus Encoded Adjuvant (AdEnA) with an Adeno-encoded antigen vaccine enhances immune responses to viral and tumor antigens, representing a potent approach to develop more effective genetic vaccines.

New-onset Thyroid Eye Disease after COVID-19 Vaccination in a Radioactive Iodine-Treated Graves' Disease Patient: A Case Report and Literature Review.

Autoimmunity associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been well-described as the mechanism of development of thyroid dysfunction following Coronavirus Disease 19 (COVID-19) infection and SARS-CoV-2 vaccination. However, the occurrence of thyroid eye disease (TED) after SARS-CoV-2 vaccination is scarcely described. The postulated mechanisms include immune reactivation, molecular mimicry and the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). We report a case of new-onset TED after receiving the SARS-CoV-2 vaccine.

Research progress of herpes zoster vaccine

Herpes zoster is a cluster blister disease that often occurs on the skin of the elderly, immunocompromised individuals and patients with chronic diseases, which is caused by the reactivation of varicella zoster virus dormant in neurons. The persistent pain of herpes zoster tortures patients and is responsible for serious mental and economic burden. With no effective drug treatment for patients, vaccination becomes more important in disease prevention. Now live attenuated vaccine and recombinant protein vaccine with adjuvant are clinically available abroad. Based on the clinical data, recombinant protein vaccine with adjuvant is the preferred one recommended by CDC.In China, many enterprises perform clinical studies on the two vaccines. However, due to the limitation of adjuvant supply, recombinant protein vaccines have not been widely provided. With the global pandemic of COVID-19, mRNA vaccine becomes a hotspot worldwide. Domestic biological enterprises should actively develop new herpes zoster vaccine to fill the vaccine vacancies in China and to enhance market competitiveness. This article briefly reviews the research progress and development of herpes zoster vaccine in various vaccine platforms.

Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses.

Subunit vaccines typically require co-administration with an adjuvant to elicit protective immunity, adding development hurdles that can impede rapid pandemic responses. To circumvent the need for adjuvant in a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine, we engineer a thermostable immunotargeting vaccine (ITV) that leverages the pan-HLA-DR monoclonal antibody 44H10 to deliver the viral spike protein receptor-binding domain (RBD) to antigen-presenting cells. X-ray crystallography shows that 44H10 binds to a conserved epitope on HLA-DR, providing the basis for its broad HLA-DR reactivity. Adjuvant-free ITV immunization in rabbits and ferrets induces robust anti-RBD antibody responses that neutralize SARS-CoV-2 variants of concern and protect recipients from SARS-CoV-2 challenge. We demonstrate that the modular nature of the ITV scaffold with respect to helper T cell epitopes and diverse RBD antigens facilitates broad sarbecovirus neutralization. Our findings support anti-HLA-DR immunotargeting as an effective means to induce strong antibody responses to subunit antigens without requiring an adjuvant.

The Role of Mucoadhesion and Mucopenetration in the Immune Response Induced by Polymer-Based Mucosal Adjuvants.

Mucus is a viscoelastic gel that acts as a protective barrier for epithelial surfaces. The mucosal vehicles and adjuvants need to pass through the mucus layer to make drugs and vaccine delivery by mucosal routes possible. The mucoadhesion of polymer particle adjuvants significantly increases the contact time between vaccine formulations and the mucosa; then, the particles can penetrate the mucus layer and epithelium to reach mucosa-associated lymphoid tissues. This review presents the key findings that have aided in understanding mucoadhesion and mucopenetration while exploring the influence of physicochemical characteristics on mucus-polymer interactions. We describe polymer-based particles designed with mucoadhesive or mucopenetrating properties and discuss the impact of mucoadhesive polymers on local and systemic immune responses after mucosal immunization. In future research, more attention paid to the design and development of mucosal adjuvants could lead to more effective vaccines.

Takayasu arteritis associated with autoimmune/inflammatory syndrome induced by adjuvants: a case-based review.

Takayasu's arteritis (TA) is a chronic granulomatous vasculitis that predominantly affects the aorta and its major branches. Despite advancements in the understanding of the pathogenic pathways of vascular inflammation, the etiology and predisposing factors of TA remain to be fully understood. In susceptible individuals, exposure to adjuvants may trigger, unlock or unmask an autoimmune disorder, presenting as non-specific constitutional symptoms or a fully developed autoimmune syndrome such as vasculitis. Here, we hypothesize that TA could be triggered by siliconosis, a subtype of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). ASIA, also known as Shoenfeld syndrome, encompasses a wide range of autoimmune and immune-mediated diseases resulting from dysregulation of the immune response after exposure to agents with adjuvant activity. This case report describes the development of large artery vasculitis, TA, in an individual one year following the placement of silicone breast implants. The patient initially presented with non-specific symptoms, and multiple imaging methods were employed, including ultrasound diagnostics, CT angiography, and 18-fluorodeoxyglucose positron emission tomography/CT. These techniques revealed vasculitic alterations in the carotid arteries and thoracic aorta. Initial treatment with glucocorticosteroids proved ineffective, prompting the addition of steroid-sparing immunosuppressive agents. Due to the distinct clinical symptoms, disease progression, implant-associated fibrosis, and resistance to therapy, the potential involvement of implants in the development of large-vessel vasculitis was considered, and a potential association with ASIA was postulated. Although there is limited evidence to support a direct link between adjuvants and the pathogenesis of TA, similarities in cellular immunity between the two conditions exist. The diagnosis of this complex and potentially debilitating condition requires a comprehensive clinical examination, laboratory evaluation, and instrumental assessment. This will aid in identifying potential contributing factors and ensuring successful treatment.

Screening of Efficient Adjuvants for the RBD-Based Subunit Vaccine of SARS-CoV-2.

The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more transmissible, with a reduced sensitivity to vaccines targeting the original virus strain. Therefore, developing an effective vaccine against both the original SARS-CoV-2 strain and its variants is an urgent need. It is known that the receptor-binding domain (RBD) in the S protein of SARS-CoV-2 is an important vaccine target, but subunit vaccines usually have lower immunogenicity and efficacy. Thus, selecting appropriate adjuvants to enhance the immunogenicity of protein-based subunit vaccine antigens is necessary. Here, an RBD-Fc subunit vaccine of SARS-CoV-2 has been generated, followed by vaccination in B6 mice, and four adjuvant regimens were investigated, including aluminum salts (Alum) + 3-O-desacyl-4'-monophosphoryl lipid A (MPL), AddaVax, QS21 + MPL, and Imiquimod. The adjuvant potency was evaluated by comparing the elicited polyclonal antibodies titers with measuring binding to RBD and S protein in ELISA and Western blot analysis, and also the cross-neutralizing antibodies titers using a pseudovirus infection assay of hACE2-expressing 293T cells, with pseudoviruses expressing the S protein of the SARS-CoV-2 original strain and Delta strain. The presence of QS21 + MPL adjuvant induced stronger polyclonal antibody response and neutralization potency blocking the original strain and Delta strain, as compared with the non-adjuvant RBD-Fc group and other adjuvant groups. Meanwhile, Imiquimod even had a negative effect in inducing specific antibodies and cross-neutralizing antibody production as an adjuvant.

Vaccine Adjuvants: Selection Criteria, Mechanism of Action Associated with Immune Responses and Future Directions.

The most effective method to minimize the prevalence of infectious diseases is vaccination. Vaccines enhance immunity and provide protection against different kinds of infections. Subunit vaccines are safe and less toxic, but due to their lower immunogenicity, they need adjuvants to boost the immune system. Adjuvants are small particles/molecules integrated into a vaccine to enhance the immunogenic feedback of antigens. They play a significant role to enhance the potency and efficiency of vaccines. There are several types of adjuvants with different mechanisms of action; therefore, improved knowledge of their immunogenicity will help develop a new generation of adjuvants. Many trials have been designed using different kinds of vaccine adjuvants to examine their safety and efficacy, but in practice, only a few have entered in animal and human clinical trials. However, for the development of safe and effective vaccines, it is important to have adequate knowledge of the side effects and toxicity of different adjuvants. The current review discussed the adjuvants which are available for producing modern vaccines as well as some new classes of adjuvants in clinical trials.

Rare Cases of Polymyalgia Rheumatica After Receiving COVID-19 Vaccinations.

Polymyalgia rheumatica (PMR) is a systemic rheumatic inflammatory disease of adults presenting with symmetrical proximal muscle stiffness and pain predominantly involving the shoulders, neck, and pelvic girdle. The coronavirus disease of 2019 (COVID-19) presented as a pandemic causing worldwide morbidity and mortality in large numbers. Rapid scientific research expedited preventative vaccine development and has helped tremendously in cutting down severe illness, hospitalizations, and death from COVID-19, with the messenger ribonucleic acid (mRNA) vaccines outperforming the others. We present two cases that showcase the incidence of polymyalgia rheumatica after receiving COVID-19 vaccination. Patient 1 is a 69-year-old female who developed arm and thigh stiffness a week before the second dose while receiving her primary Moderna vaccine series. She had an elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), so she was started on low-dose steroids, which were weaned down over a five-month period. Three weeks after receiving her Moderna booster, she had a recurrence of the classic polymyalgia rheumatica symptoms and elevated ESR. She responded to prednisone 15 mg with a successful taper over eight months. Patient 2 is a 74-year-old male who received his primary series and booster through Pfizer-BioNTech. Prior to the booster, he was treated for COVID-19 with monoclonal antibody therapy. He presented to the office with hip and shoulder pain and stiffness along with an elevated C-reactive protein. Consequently, he received 20 mg of prednisone but needed to increase his dose to 25 mg total to help with the control of his inflammation. The goal of this article is to prompt physicians about the possibility of PMR incidence after patients receive vaccinations for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PMR can be debilitating to the quality of life of patients. Knowing this association allows for more timely and competent treatment. PMR following SARS-CoV-2 vaccinations is continuously being observed in the medical field. Increased knowledge may help prevent the recurrence with subsequent doses. Further studies on the follow-up of such cases and the effect on subsequent immunization would be helpful.

Lipid-Based Poly(I:C) Adjuvants Strongly Enhance the Immunogenicity of SARS-CoV-2 Receptor-Binding Domain Vaccine

Background The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has greatly threatened public health. Recent studies have revealed that the spike receptor-binding domain (RBD) of SARS-CoV-2 is a potent target for vaccine development. However, adjuvants are usually required to strengthen the immunogenicity of recombinant antigens. Different types of adjuvants can elicit different immune responses. Methods We developed an RBD recombinant protein vaccine with a polyriboinosinic acid-polyribocytidylic acid [poly(I:C)] adjuvant to evoke a strong immune response. The delivery of poly(I:C) was optimized in two steps. First, poly(I:C) was complexed with a cationic polymer, poly-l-lysine (PLL), to form poly(I:C)-PLL, a polyplex core. Thereafter, it was loaded into five different lipid shells (group II, III-1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC], III-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine [DOPE], IV-DOPE, and IV-DSPC). We performed an enzyme-linked immunosorbent assay and enzyme-linked immunosorbent spot assay to compare the ability of the five lipopolyplex adjuvants to enhance the immunogenicity of the SARS-CoV-2 RBD protein, including humoral and cellular immune responses. Finally, the adjuvant with the highest immunogenicity was selected to verify the protective immunity of the vaccine through animal challenge experiments. Results Recombinant RBD protein has low immunogenicity. The different adjuvants we developed enhanced the immunogenicity of the RBD protein in different ways. Among the lipopolyplexes, those containing DOPE (III-DOPE and IV-DOPE) elicited RBD-specific immunoglobulin G antibody responses, and adjuvants with four components elicited better RBD-specific immunoglobulin G antibody responses than those containing three components (P < 0.05). The IC50 and IC90 titers indicated that the IV-DOPE lipopolyplex had the greatest neutralization ability, with IC50 titers of 1/117,490. Furthermore, in the challenge study, IV-DOPE lipopolyplex protected mice from SARS-CoV-2 infection. On the fourth day after infection, the average animal body weights were reduced by 18.56% (24.164 ± 0.665 g vs. 19.678 ± 0.455 g) and 0.06% (24.249 ± 0.683 g vs. 24.235 ± 0.681 g) in the MOCK and vaccine groups, respectively. In addition, the relative expression of viral RNA in the vaccinated group was significantly lower than that in the MOCK group (P < 0.05). Interstitial inflammatory cell infiltration was observed in the MOCK group, whereas no obvious damage was observed in the vaccinated group. Conclusions The IV-DOPE-adjuvanted SARS-CoV-2 recombinant RBD protein vaccine efficiently protected mice from SARS-CoV-2 in the animal challenge study. Therefore, IV-DOPE is considered an exceptional adjuvant for SARS-CoV-2 recombinant RBD protein-based vaccines and has the potential to be further developed into a SARS-CoV-2 recombinant RBD protein-based vaccine. © Wolters Kluwer Health, Inc. All rights reserved.

Functionalization of nanobiomaterials in nanovaccinology

Nanovaccines are highly efficient for the treatment of many diseases due to their exact biochemical interactions and active constituents in it. Vaccinations are the best preventive technique used against infectious diseases. To synthesize highly potential vaccines, there is a need to develop new adjuvants and delivery system that improve immunogenicity. Applications of nanotechnology in vaccine synthesis helps to improve the applications based on it. Vaccinations are most efficient preventive measure against infectious diseases. Presently Covid 19 vaccines are on high demand. But still, vaccine hesitance is present in many countries. Vaccine hesitance about COVID-19 virus results from unjustified fear of hypothetical side effects of vaccines and the lack of trust of vaccine safety and efficacy. Nowadays, vaccine development is evolving at a high rate, and the number of candidate vaccine is progressively increasing day by day. This review analyzes the new approach of functionalized bionanomaterial-based nanovaccines and their applications. © 2022 Scrivener Publishing LLC. All rights reserved.

Montelukast and coronavirus disease 2019: a scoping review

Coronavirus disease 2019 (COVID-19) is an emerging worldwide issue, that has affected a large number of people around the world. So far, many studies have aimed to develop a therapeutic approach against COVID-19. Montelukast (MK) is a safe asthma controller drug, which is considered as a potential antiviral drug for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review has a systematic approach to investigate the reports on the use of MK as a part of treatment or a prophylactic agent in COVID-19. The search was conducted in PubMed, Web of Science, and Scopus databases and yielded 35 studies containing the influence of MK on SARS-CoV-2. Ultimately, MK appears to be worth being used as an adjuvant therapeutic and prophylactic drug against SARS-CoV-2. Nevertheless, more clinical trials are required to accurately investigate its effectiveness.

An Immunoinformatics Approach to Design Novel and Potent Multi-Epitope-Based Vaccine to Target Lumpy Skin Disease

The lumpy skin disease (LSD) virus of the Poxviridae family is a serious threat that mostly affects cattle and causes significant economic loss. LSD has the potential to spread widely and its rapidly across borders. Despite the availability of information, there is still no competitive vaccine available for LSD. Therefore, the current study was conducted to develop an epitope-based LSD vaccine that is efficient, secure, and biocompatible and stimulates both innate and adaptive immune responses using immunoinformatics techniques. Initially, putative virion core proteins were manipulated;B-cell and T-cell epitopes have been predicted and connected with the help of adjuvants and linkers. Numerous bioinformatics methods, including antigenicity testing, transmembrane topology screening, allergenicity assessment, conservancy analysis, and toxicity evaluation, were employed to find superior epitopes. Based on promising vaccine candidates and immunogenic potential, the vaccine design was selected. Strong interactions between TLR4 and TLR9 and the anticipated vaccine design were revealed by molecular docking. Finally, based on the high docking score, computer simulations were performed in order to assess the stability, efficacy, and compactness of the constructed vaccine. The simulation outcomes showed that the polypeptide vaccine design was remarkably stable, with high expression, stability, immunogenic qualities, and considerable solubility. Additionally, computer-based research shows that the constructed vaccine provides adequate population coverage, making it a promising candidate for use in the design of vaccines against other viruses within the Poxviridae family and potentially other virus families as well. These outcomes suggest that the epitope-based vaccine developed in this study will be a significant candidate against LSD to control and prevent LSDV-related disorders if further investigated experimentally.

Nanovaccines against Viral Infectious Diseases.

Infectious diseases have always been regarded as one of the greatest global threats for the last century. The current ongoing COVID-19 pandemic caused by SARS-CoV-2 is living proof that the world is still threatened by emerging infectious diseases. Morbidity and mortality rates of diseases caused by Coronavirus have inflicted devastating social and economic outcomes. Undoubtedly, vaccination is the most effective method of eradicating infections and infectious diseases that have been eradicated by vaccinations, including Smallpox and Polio. To date, next-generation vaccine candidates with novel platforms are being approved for emergency use, such as the mRNA and viral vectored vaccines against SARS-CoV-2. Nanoparticle based vaccines are the perfect candidates as they demonstrated targeted antigen delivery, improved antigen presentation, and sustained antigen release while providing self-adjuvanting functions to stimulate potent immune responses. In this review, we discussed most of the recent nanovaccines that have found success in immunization and challenge studies in animal models in comparison with their naked vaccine counterparts. Nanovaccines that are currently in clinical trials are also reviewed.

Synergistic Activity of Colistin in Combination with Clofoctol against Colistin Resistant Gram-Negative Pathogens.

Colistin is a bactericidal antibiotic identified decades ago which is active against a number of Gram-negative pathogens. After early elimination from clinical use due to toxicity issues, colistin has been reintroduced as a last-resort treatment for antibiotic-resistant Gram-negative infections lacking other therapeutic options. Inevitably, colistin resistance has emerged among clinical isolates, making the development of colistin adjuvants extremely beneficial. Clofoctol is a synthetic antibiotic active against Gram-positive bacteria, with low toxicity and high tropism for the airways. Interestingly, clofoctol has been found to have multiple biological activities and has been proposed for the treatment of several obstructive lung diseases, including asthma, lung cancer, and SARS-CoV-2 infection. In this study, the activity of clofoctol as a colistin adjuvant was investigated in Gram-negative lung pathogens that are critical for the high prevalence of multidrug-resistant isolates, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Clofoctol potentiated the bactericidal effect of colistin in all tested strains and reduced colistin MICs below the susceptibility breakpoint in nearly all colistin-resistant strains. Overall, this observation supports the development of inhaled clofoctol-colistin formulations for the treatment of difficult-to-treat airway infections caused by Gram-negative pathogens. IMPORTANCE Colistin is used as a last-resort antibiotic against extensively drug-resistant Gram-negative pathogens. However, colistin resistance is on the rise. Clofoctol is an antibiotic used against Gram-positive bacteria, with low toxicity and high penetration and storage in the airways. Here, a strong synergistic activity of the colistin-clofoctol combination against colistin-resistant Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii isolates is reported, supporting the development of clofoctol-colistin formulations for the therapy of difficult-to-treat airways infections caused by these Gram-negative pathogens.