Ear abnormalities in chronic fatigue syndrome (CFS), fibromyalgia (FM), Coronavirus-19 infectious disease (COVID) and long-COVID syndrome (PCS), sick-building syndrome (SBS), post-orthostatic tachycardia syndrome (PoTS), and autoimmune/inflammatory syndrome induced by adjuvants (ASIA): A systematic review.

Chronic fatigue syndrome (CFS), fibromyalgia (FM), silicone breast implants (SBI), Coronavirus-19 infectious disease (COVID), COVID-19 vaccination (post-COVIDvac-syndrome), Long-COVID syndrome (PCS), sick-building syndrome (SBS), post-orthostatic tachycardia syndrome (PoTS), and autoimmune/ inflammatory syndrome induced by adjuvants (ASIA) are a cluster of poorly understood medical conditions that have in common a group of ill-defined symptoms and dysautonomic features. Most of the clinical findings of this group of diseases are unspecific, such as fatigue, diffuse pain, cognitive impairment, paresthesia, tachycardia, anxiety, and depression. Hearing disturbances and vertigo have also been described in this context, the underlying pathophysiologic process for these conditions might rely on autonomic autoimmune dysbalance. The authors procced a literature review regarding to hearing and labyrinthic disturbances in CSF, FM, SBI, COVID, post-COVIDvac-syndrome, PCS, SBS, POTS, and ASIA. The PRISMA guidelines were followed, and the literature reviewed encompassed papers from January 1990 to January 2024. After the initial evaluation of the articles found in the search through Pubmed, Scielo and Embase, a total of 172 articles were read and included in this review. The prevalence of hearing loss, dizziness, vertigo and tinnitus was described and correlated with the diseases investigated in this study. There are great variability in the frequencies of symptoms found, but cochlear complaints are the most frequent in most studies. Vestibular symptoms are less reported. The main pathophysiological mechanisms are discussed. Direct effects of the virus in the inner ear or nervous pathways, impaired vascular perfusion, cross-reaction or autoimmune immunoreactivity, oxidative stress, DNA methylation, epigenetic modifications and gene activation were implicated in the generation of the investigated symptoms. In clinical practice, all patients with these autoimmune conditions who have any audiological complaint an ENT consultation followed by an audiometry are needed.

Chimeric lipoproteins for leptospirosis vaccine: immunogenicity and protective potential.

Leptospirosis, a neglected zoonotic disease, is caused by pathogenic spirochetes belonging to the genus Leptospira and has one of the highest morbidity and mortality rates worldwide. Vaccination stands out as one of the most effective preventive measures for susceptible populations. Within the outer membrane of Leptospira spp., we find the LIC12287, LIC11711, and LIC13259 lipoproteins. These are of interest due to their surface location and potential immunogenicity. Thorough examination revealed the conservation of these proteins among pathogenic Leptospira spp.; we mapped the distribution of T- and B-cell epitopes along their sequences and assessed the 3D structures of each protein. This information aided in selecting immunodominant regions for the development of a chimeric protein. Through gene synthesis, we successfully constructed a chimeric protein, which was subsequently expressed, purified, and characterized. Hamsters were immunized with the chimeric lipoprotein, formulated with adjuvants aluminum hydroxide, EMULSIGEN®-D, Sigma Adjuvant System®, and Montanide™ ISA206VG. Another group was vaccinated with an inactivated Escherichia coli bacterin expressing the chimeric protein. Following vaccination, hamsters were challenged with a virulent L. interrogans strain. Our evaluation of the humoral immune response revealed the production of IgG antibodies, detectable 28 days after the second dose, in contrast to pre-immune samples and control groups. This demonstrates the potential of the chimeric protein to elicit a robust humoral immune response; however, no protection against challenge was achieved. While this study provides valuable insights into the subject, further research is warranted to identify protective antigens that could be utilized in the development of a leptospirosis vaccine. KEY POINTS: • Several T- and B-cell epitopes were identified in all the three proteins. • Four different adjuvants were used in vaccine formulations. • Immunization stimulated significant levels of IgG2/3 in vaccinated animals.

Functional chia (Salvia hispanica L.) co-product protein hydrolysate: An analysis of biochemical, antidiabetic, antioxidant potential and physicochemical properties.

Protein hydrolysates with antioxidant potential have been reported to act as adjuvants in preventing and treating type-2 diabetes (T2D). This work investigated the biochemical, antidiabetic, antioxidant potential, and physicochemical properties of chia meal protein hydrolysate (CMPH). Bands smaller than 14 kDa were observed in the electrophoretic profile. The predominant amino acids were hydrophobic and aromatic. CMPH had the potential to inhibit α-amylase (IC50: 1.76 ± 0.13 mg/mL), α-glucosidase (IC50: 0.42 ± 0.13 mg/mL), and DPP-IV (IC50: 0.46 ± 0.14 mg/mL). Antioxidant activity for ABTS (IC50: 0.236 mg/mL), DPPH (8.83 ± 0.52%), and ORAC (IC25: 0.115 mg/mL). Against chia meal protein isolate (CMPI), CMPH has a broad solubility (pH 2-12.46). Particle size (624.5 ± 247.3 nm), low PDI (0.22 ± 0.06), ζ-potential (-31.1 ± 2.5 mV), and surface hydrophobicity (11,183.33 ± 2024.11) and the intrinsic fluorescence peak of CMPH was lower than that of CMPI. CMPH represents an alternative to add value to the agri-food co-product of the chia seed oil industry, generating food ingredients with outstanding antidiabetic and antioxidant potential.

Hybrid response to SARS-CoV-2 and Neisseria meningitidis C after an OMV-adjuvanted immunization in mice and their offspring.

COVID-19, caused by SARS-CoV-2, and meningococcal disease, caused by Neisseria meningitidis, are relevant infectious diseases, preventable through vaccination. Outer membrane vesicles (OMVs), released from Gram-negative bacteria, such as N. meningitidis, present adjuvant characteristics and may confer protection against meningococcal disease. Here, we evaluated in mice the humoral and cellular immune response to different doses of receptor binding domain (RBD) of SARS-CoV-2 adjuvanted by N. meningitidis C:2a:P1.5 OMVs and aluminum hydroxide, as a combined preparation for these pathogens. The immunization induced IgG antibodies of high avidity for RBD and OMVs, besides IgG that recognized the Omicron BA.2 variant of SARS-CoV-2 with intermediary avidity. Cellular immunity showed IFN-γ and IL-4 secretion in response to RBD and OMV stimuli, demonstrating immunologic memory and a mixed Th1/Th2 response. Offspring presented transferred IgG of similar levels and avidity as their mothers. Humoral immunity did not point to the superiority of any RBD dose, but the group immunized with a lower antigenic dose (0.5 µg) had the better cellular response. Overall, OMVs enhanced RBD immunogenicity and conferred an immune response directed to N. meningitidis too.

Hypothetical adhesin CAM87009.1 formulated in alum or biogenic silver nanoparticles protects mice from lethal infection by multidrug-resistant Acinetobacter baumannii.

Due to its antimicrobial resistance characteristics, the World Health Organization (WHO) classifies A. baumannii as one of the critical priority pathogens for the development of new therapeutic strategies. Vaccination has been approached as an interesting strategy to overcome the lack of effective antimicrobials and the long time required to develop and approve new drugs. In this study, we aimed to evaluate as a vaccine the hypothetical adhesin protein CAM87009.1 in its recombinant format (rCAM87009.1) associated with aluminum hydroxide (Alhydrogel®) or biogenic silver nanoparticles (bio-AgNP) as adjuvant components against lethal infection by A. baumannii MDR strain. Both vaccine formulations were administered in three doses intramuscularly in BALB/c murine models and the vaccinated animals were tested in a challenge assay with A. baumannii MDR strain (DL100). rCAM87009.1 protein associated with both adjuvants was able to protect 100 % of animals challenged with the lethal strain during the challenge period. After the euthanasia of the animals, no A. baumannii colonies were detected in the lungs of animals vaccinated with the rCAM87009.1 protein in both formulations. Since the first immunization, high IgG antibody titers were observed (1:819,200), with results being statistically similar in both vaccine formulations evaluated. rCAM87009.1 associated with both adjuvants was capable of inducing at least one class of isotypes associated with the processes of neutralization (IgG2b and IgA for bio-AgNP and Alhydrogel®, respectively), opsonization (IgG1 in both vaccines) and complement activation (IgM and IgG3 for bio-AgNP and Alhydrogel®, respectively). Furthermore, reduced tissue damage was observed in animals vaccinated with rCAM87009.1 + bio-AgNP when compared to animals vaccinated with Alhydrogel®. Our results indicate that the rCAM87009.1 protein associated with both bio-AgNP and Alhydrogel® are combinations capable of promoting immunity against infections caused by A. baumannii MDR. Additionally, we demonstrate the potential of silver nanoparticles as alternative adjuvant molecules to the use of aluminum salts.

Nanocarriers of antigen proteins for vaccine delivery.

Nanoformulations in vaccinology provide antigen stability and enhanced immunogenicity, in addition to providing targeted delivery and controlled release. In the last years, much research has been focused on vaccine development using virus-like particles, liposomes, emulsions, polymeric, lipid, and inorganic nanoparticles. Importantly, nanoparticle interactions with innate and adaptive immune systems must be clearly understood to guide the rational development of nanovaccines. This review provides a recap and updates on different aspects advocating nanoparticles as promising antigen carriers and immune cell activators for vaccination. Moreover, it offers a discussion of how the physicochemical properties of nanoparticles are modified to target specific cells and improve vaccine efficacy.

Long-term antigen-specific immune response by an oncolytic adenovirus encoding SP-SA-E7-4-1BBL in HPV-16 cancer model.

BACKGROUND: To describe an oncolytic adenovirus (OAd) encoding SP-SA-E7-4-1BBL that is capable of inducing tumor regression in therapeutic assays. Herein, we tested whether the antitumor effect is given by the induction of a tumor-specific immune response, as well as the minimum dose needed to elicit antitumor protection and monitor the OAd biodistribution over time. METHODS AND RESULTS: C57BL/6 mice (n = 5) per group were immunized twice with OAds encoding SP-SA-E7-4-1BBL, SA-E7-4-1BBL, or SP-SA-4-1BBL and challenged with TC-1 cancer cells. The DNA construct SP-SA-E7-4-1BBL was employed as a control via biolistic or PBS injection. Groups without tumor development at 47 days were rechallenged with TC-1 cells, and follow-up lasted until day 90. The minimum dose of OAd to induce the antitumor effect was established by immunization using serial dilution doses. The cytometry bead assay and the ELISpot assay were used to evaluate cytokine release in response to ex vivo antigenic stimulation. The distribution profile of the OAd vaccine was evaluated in the different organs by histological, immunohistochemical and qPCR analyses. The OAd SP-SA-E7-4-1BBL-immunized mice did not develop tumors even in a rechallenge. A protective antitumor effect was observed from a dose that is one hundredth of most reports of adenoviral vaccines. Immunization with OAd increases Interferon-gamma-producing cells in response to antigen stimulation. OAd was detected in tumors over time, with significant morphological changes, contrary to nontumor tissues. CONCLUSIONS: The OAd SP-SA-E7-4-1BBL vaccine confers a prophylactic, safe, long-lasting, and antigen-dependent antitumor effect mediated by a Th1 antitumor immune response.

Corrigendum: Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants.

[This corrects the article DOI: 10.3389/fimmu.2024.1307546.].

Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants.

Zika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_ΔSTP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_ΔSTP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-ΔSTP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_ΔSTP+Alum protected adult mice upon viral challenge. Collectively, the ZK_ΔSTP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies.

Autoimmune Autoinflammatory Syndrome Induced by Adjuvants (ASIA) After Injection of Foreign Materials for Cosmetic Purposes: Retrospective Analysis of 1027 Cases.

BACKGROUND: The injection of illicit, non-regulated foreign materials may trigger an autoimmune autoinflammatory syndrome induced by adjuvants (ASIA). METHODS: A retrospective review of health records was performed to identify patients' epidemiological and clinical characteristics. The issues analyzed were age and gender of cases, occupation, the person who administered the substance, anatomical site, type and volume of the injected substance, time from injection to the onset of symptoms, chief complaint, measures taken to alleviate symptoms, local complications, systemic manifestations, and imaging method to aid in diagnosis. RESULTS: More than 70% of patients were female and dedicated to household activities; the mean age was 44 years for females and 40.7 years for males. One-quarter of patients reported some comorbidity. The most commonly reported substance was mineral oil, whereas the most frequent anatomical site was the gluteal region with volumes around one liter. Signs and symptoms occurred almost exclusively at a local level, pain (40%) and swelling (18%) being the predominant manifestations with a peak incidence after three years. Treatment was mainly medical; surgery, primarily en bloc resection, was performed in 20% of patients. CONCLUSIONS: A myriad of substances may induce autoimmune autoinflammatory syndrome induced by adjuvants (ASIA) when injected for cosmetic purposes. Since effective treatments are scarce, public policies should be enforced to alert the community and limit the consequences of this healthcare problem. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Anestesia libre de opioides en cirugía bariátrica laparoscópica

Introducción: La anestesia libre de opioides surge de las alternativas farmacológicas que permiten otra opción anestésica en el arsenal del anestesiólogo. Objetivo: Evaluar la efectividad y seguridad de una técnica anestésica libre de opioides en el paciente intervenido con cirugía bariátrica laparoscópica. Métodos: Se realizó un estudio observacional analítico, prospectivo y longitudinal en 23 pacientes operados con anestesia general multimodal libre de opioides. Pacientes mayores de 18 años con un índice de masa corporal mayor o igual a 35 kg/m2, con estado físico ASA II y III. Se evaluó la analgesia posoperatoria e intraoperatoria como una necesidad de la analgesia de rescate en el tiempo de recuperación y los efectos adversos. Resultados: Se demostró que la edad promedio fue 38,19 ± 8,73 con un predominio en el sexo femenino, los pacientes fueron clasificados como ASA II y obesos grados III. Hubo una estabilidad hemodinámica intraoperatoria. El 82,6 % de los pacientes no presentaron dolor posoperatorio en las primeras 24 h. No se presentaron pacientes con dolor severo. Requirieron analgesia de rescate cinco pacientes (21,7 %) en posoperatorio, y las complicaciones fueron escasas sin repercusión clínica. El tiempo promedio para la extubación fue de 6,7 ± 0,8 min y la recuperación total de 29,6 ± 0,8 min. Conclusiones: La técnica multimodal libre de opioides resultó segura y efectiva, con un adecuado estado de analgesia perioperatoria y escasas complicaciones en los pacientes intervenido con cirugía bariátrica laparoscópica.

Introduction: Opioid-free anesthesia arises from pharmacological alternatives that allow another anesthetic option in the anesthesiologist's arsenal. Objective: To evaluate the effectiveness and safety of an opioid-free anesthetic technique in patients undergoing laparoscopic bariatric surgery. Methods: An analytical, prospective and longitudinal observational study was carried out in 23 patients operated on with opioid-free multimodal general anesthesia. The patients studied were over 18 years of age, with a body mass index greater than or equal to 35 kg/m2, ASA physical status II and III. Postoperative and intraoperative analgesia were evaluated as a need for rescue analgesia in recovery time and adverse effects. Results: It was shown that the average age was 38.19 ± 8.73 with a predominance in the female sex, the patients were classified as ASA II and grade III obese. There was intraoperative hemodynamic stability. 82.6% of patients did not experience postoperative pain in the first 24 hours. There were no patients with severe pain. Five patients (21.7%) required rescue analgesia postoperatively, and complications were rare without clinical repercussions. The average time for extubation was 6.7 ± 0.8 min and total recovery was 29.6 ± 0.8 min. Conclusions: The opioid-free multimodal technique was safe and effective, with adequate state of perioperative analgesia and few complications in patients undergoing laparoscopic bariatric surgery.

Evaluation of three formulations based on Polymorphic membrane protein D in mice infected with Chlamydia trachomatis.

The significant impact of Chlamydia trachomatis(Ct) infections worldwide highlights the need to develop a prophylactic vaccine that elicits effective immunity and protects the host from the immunopathological effects of Ct infection. The aim of this study was to evaluate a vaccine based on a fragment of the Polymorphic membrane protein D (FPmpD) of C. trachomatis as an immunogen using a heterologous DNA prime-protein boost strategy in female mice Three different formulations were evaluated as protein boost: free recombinant FPmpD (rFPmpD) or rFPmpD formulated with a liposomal adjuvant alternatively supplemented with CpG or a cationic gemini lipopeptide as immunostimulants. The three candidates induced an increase in the cervicovaginal and systemic titers of anti-rFPmpD antibodies in two strains of mice (BALB/c and C57BL/6), with no evidence of fertility alterations. The three formulations induced a rapid and robust humoral immune response upon the Ct challenge. However, the booster with free rFPmpD more efficiently reduced the shedding of infective Ct and prevented the development of immunopathology. The formulations containing adjuvant induced a strong inflammatory reaction in the uterine tissue. Hence, the prime-boost strategy with the adjuvant-free FPmpD vaccine formulation might constitute a promissory candidate to prevent C. trachomatis intravaginal infection.

Surface immunogenic protein from Streptococcus agalactiae and Fissurella latimarginata hemocyanin are TLR4 ligands and activate MyD88- and TRIF dependent signaling pathways.

The development of vaccine adjuvants is of interest for the management of chronic diseases, cancer, and future pandemics. Therefore, the role of Toll-like receptors (TLRs) in the effects of vaccine adjuvants has been investigated. TLR4 ligand-based adjuvants are the most frequently used adjuvants for human vaccines. Among TLR family members, TLR4 has unique dual signaling capabilities due to the recruitment of two adapter proteins, myeloid differentiation marker 88 (MyD88) and interferon-ß adapter inducer containing the toll-interleukin-1 receptor (TIR) domain (TRIF). MyD88-mediated signaling triggers a proinflammatory innate immune response, while TRIF-mediated signaling leads to an adaptive immune response. Most studies have used lipopolysaccharide-based ligands as TLR4 ligand-based adjuvants; however, although protein-based ligands have been proven advantageous as adjuvants, their mechanisms of action, including their ability to undergo structural modifications to achieve optimal immunogenicity, have been explored less thoroughly. In this work, we characterized the effects of two protein-based adjuvants (PBAs) on TLR4 signaling via the recruitment of MyD88 and TRIF. As models of TLR4-PBAs, we used hemocyanin from Fissurella latimarginata (FLH) and a recombinant surface immunogenic protein (rSIP) from Streptococcus agalactiae. We determined that rSIP and FLH are partial TLR4 agonists, and depending on the protein agonist used, TLR4 has a unique bias toward the TRIF or MyD88 pathway. Furthermore, when characterizing gene products with MyD88 and TRIF pathway-dependent expression, differences in TLR4-associated signaling were observed. rSIP and FLH require MyD88 and TRIF to activate nuclear factor kappa beta (NF-κB) and interferon regulatory factor (IRF). However, rSIP and FLH have a specific pattern of interleukin 6 (IL-6) and interferon gamma-induced protein 10 (IP-10) secretion associated with MyD88 and TRIF recruitment. Functionally, rSIP and FLH promote antigen cross-presentation in a manner dependent on TLR4, MyD88 and TRIF signaling. However, FLH activates a specific TRIF-dependent signaling pathway associated with cytokine expression and a pathway dependent on MyD88 and TRIF recruitment for antigen cross-presentation. Finally, this work supports the use of these TLR4-PBAs as clinically useful vaccine adjuvants that selectively activate TRIF- and MyD88-dependent signaling to drive safe innate immune responses and vigorous Th1 adaptive immune responses.

Toxicological Effects of Thimerosal and Aluminum in the Liver, Kidney, and Brain of Zebrafish (Danio rerio).

Vaccination programs in the first years of a child's life are effective and extremely important strategies for the successful eradication of diseases. However, as no intervention is without risks, the metal-based components of some vaccines, such as thimerosal (TMS), a preservative composed of ethylmercury, and aluminum (Al), have begun to generate distrust on the part of the population. Therefore, this study evaluated the effects of exposure to thimerosal and aluminum hydroxide (alone or in mixture) on Danio rerio (zebrafish) specimens. The fish were exposed to thimerosal and/or aluminum hydroxide intraperitoneally. The liver, kidney, and brain were removed for a biochemical biomarker analysis, histopathological analysis, and metal quantification. As a result, we observed changes in the activity of the analyzed enzymes (SOD, GST, GPx) in the kidney and brain of the zebrafish, a reduction in GSH levels in all analyzed tissues, and a reduction in MT levels in the kidney and liver as well as in the brain. Changes in AChE enzyme activity were observed. The biochemical results corroborate the changes observed in the lesion index and histomorphology sections. We emphasize the importance of joint research on these compounds to increase the population's safety against their possible toxic effects.

Heterologous DNA Prime- Subunit Protein Boost with Chikungunya Virus E2 Induces Neutralizing Antibodies and Cellular-Mediated Immunity.

Chikungunya virus (CHIKV) has become a significant public health concern due to the increasing number of outbreaks worldwide and the associated comorbidities. Despite substantial efforts, there is no specific treatment or licensed vaccine against CHIKV to date. The E2 glycoprotein of CHIKV is a promising vaccine candidate as it is a major target of neutralizing antibodies during infection. In this study, we evaluated the immunogenicity of two DNA vaccines (a non-targeted and a dendritic cell-targeted vaccine) encoding a consensus sequence of E2CHIKV and a recombinant protein (E2*CHIKV). Mice were immunized with different homologous and heterologous DNAprime-E2* protein boost strategies, and the specific humoral and cellular immune responses were accessed. We found that mice immunized with heterologous non-targeted DNA prime- E2*CHIKV protein boost developed high levels of neutralizing antibodies, as well as specific IFN-γ producing cells and polyfunctional CD4+ and CD8+ T cells. We also identified 14 potential epitopes along the E2CHIKV protein. Furthermore, immunization with recombinant E2*CHIKV combined with the adjuvant AS03 presented the highest humoral response with neutralizing capacity. Finally, we show that the heterologous prime-boost strategy with the non-targeted pVAX-E2 DNA vaccine as the prime followed by E2* protein + AS03 boost is a promising combination to elicit a broad humoral and cellular immune response. Together, our data highlights the importance of E2CHIKV for the development of a CHIKV vaccine.

New Onset Autoimmune Diseases after the Sputnik Vaccine.

The vertiginous advance for identifying the genomic sequence of SARS-CoV-2 allowed the development of a vaccine including mRNA-based vaccines, inactivated viruses, protein subunits, and adenoviral vaccines such as Sputnik. This study aims to report on autoimmune disease manifestations that occurred following COVID-19 Sputnik vaccination. Patients and Methods: A retrospective study was conducted on patients with new-onset autoimmune diseases induced by a post-COVID-19 vaccine between March 2021 and December 2022, in two referral hospitals in Mexico City and Argentina. The study evaluated patients who received the Sputnik vaccine and developed recent-onset autoimmune diseases. Results: Twenty-eight patients developed recent-onset autoimmune diseases after Sputnik vaccine. The median age was 56.9 ± 21.7 years, with 14 females and 14 males. The autoimmune diseases observed were neurological in 13 patients (46%), hematological autoimmune manifestations occurred in 12 patients (42%), with thrombotic disease observed in 10 patients (28%), and autoimmune hemolytic anemia in two patients (7.1%). Rheumatological disorders were present in two patients (7.1%), and endocrine disorders in one patient (3.5%). Principio del formulario Conclusion: Although the COVID-19 Sputnik vaccine is generally safe, it can lead to adverse effects. Thrombosis and Guillain-Barre were the most frequent manifestations observed in our group of patients.

Challenges and Strategies for Developing Recombinant Vaccines against Leptospirosis: Role of Expression Platforms and Adjuvants in Achieving Protective Efficacy.

The first leptospiral recombinant vaccine was developed in the late 1990s. Since then, progress in the fields of reverse vaccinology (RV) and structural vaccinology (SV) has significantly improved the identification of novel surface-exposed and conserved vaccine targets. However, developing recombinant vaccines for leptospirosis faces various challenges, including selecting the ideal expression platform or delivery system, assessing immunogenicity, selecting adjuvants, establishing vaccine formulation, demonstrating protective efficacy against lethal disease in homologous challenge, achieving full renal clearance using experimental models, and reproducibility of protective efficacy against heterologous challenge. In this review, we highlight the role of the expression/delivery system employed in studies based on the well-known LipL32 and leptospiral immunoglobulin-like (Lig) proteins, as well as the choice of adjuvants, as key factors to achieving the best vaccine performance in terms of protective efficacy against lethal infection and induction of sterile immunity.

ASIA and BIA-ALCL as adverse reactions to silicone breast implants / ASIA e BIA-ALCL como reações adversas aos implantes mamários de silicone

Adjuvant-induced autoimmune/inflammatory syndrome leads to capsular contracture and fibrosis from the oxidation that takes place in silicone. Anaplastic large cell lymphoma occurs through the development of a seroma, with the formation of a periprosthetic effusion, or through the infiltration of the condition itself. To analyze these conditions, a review of the literature was carried out on the symptoms and pathophysiology of the autoimmune/inflammatory syndrome induced by adjuvants and anaplastic large cell lymphoma, searched using the terms "ASIA breast silicone," "Lymphoma," "Adjuvants" "Immunologic" " Breast Implants" on the PubMed platform. Analyzing the data obtained, it was noted that the symptoms of the autoimmune/inflammatory syndrome induced by adjuvants are nonspecific, such as fatigue, myalgia, arthralgia, morning stiffness, and night sweats, and therefore need attention. Anaplastic large cell lymphoma presents with breast pain, periprosthetic effusion, and palpable mass, among other characteristics. Because of these aspects, it is concluded that a good investigation should be carried out when nonspecific symptoms appear, regardless of the time the surgery was performed since these complications can occur years later.

A síndrome autoimune/inflamatória induzida por adjuvantes leva à contratura capsular e fibrose pela oxidação que acontece no silicone. O linfoma anaplásico de grandes células ocorre através do desenvolvimento de um seroma, com a formação de derrame periprotético ou por uma infiltração da própria afecção. Para análise destes acometimentos, foi realizada uma revisão da literatura acerca da sintomatologia e fisiopatologia da síndrome autoimune/inflamatória induzida por adjuvantes e linfoma anaplásico de grandes células, pesquisada através dos termos "ASIA breast silicone" "Lymphoma" "Adjuvants" "Immunologic" "Breast Implants" na plataforma PubMed. Analisando os dados obtidos, notou-se que os sintomas da síndrome autoimune/inflamatória induzida por adjuvantes são inespecíficos, como fadiga, mialgia, artralgia, rigidez matinal e suores noturnos, e, portanto, necessitam de atenção. Já o linfoma anaplásico de grandes células se apresenta com dor mamária, derrame periprotético, massa palpável, dentre outras características. Em vista destes aspectos, conclui-se que uma boa investigação deve ser realizada ao surgirem sintomas inespecíficos, independentemente do tempo que a cirurgia foi realizada, uma vez que estas complicações podem ocorrer anos após a cirurgia.