High Levels Of IgG Antibodies Research Articles

Comparison of immune response parameters between homologous and heterologous COVID-19 vaccines: A scoping review

It has been over 4 years since the emergence of the coronavirus disease 2019 (COVID-19) pandemic. This highly contagious respiratory infection has endangered the health of millions and significantly impacted healthcare systems and economies. Vaccines are believed to confer immunity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, reducing both the severity of infection and the spread of the virus. Within a short period, various COVID-19 vaccines were developed and extensively tested before being approved by the WHO for distribution and administration. Now, due to concerns about emerging new strains of the virus and limited vaccine availability, a heterologous vaccine strategy is being deployed. Therefore, this paper aims to conduct a scoping review of existing evidence to compare the immunogenicity of heterologous vaccines with homologous vaccines and determine which confers better immunity against COVID-19. A literature search was conducted across three electronic databases (Ovid MEDLINE, PubMed, and Scopus). The retrieved studies were screened for relevance and eligibility using the online platform Covidence. A total of 31 articles were shortlisted for data extraction and analysis. Among these, 21 were observational studies, and 10 were clinical trials. The analysis demonstrated that participants who received heterologous vaccination regimens generated higher levels of IgG antibodies against the spike protein of SARS-CoV-2, antibodies targeting the receptor-binding domain, and T-cell responses compared to those who received homologous vaccination regimens. Furthermore, heterologous vaccination produced higher titers of neutralizing antibodies against several variants of concern (VOC), including Alpha, Beta, Gamma, Delta, and Omicron. No severe vaccine-related adverse events were reported in these studies, and common local and systemic side effects were manageable. Overall, heterologous vaccination regimes induced strong humoral and cellular immunity, comparable to homologous vaccination regimes, with stronger neutralizing antibody activity against VOCs.

Evaluation of Antibody Response and Reinfection in Improved Hypertensive, Cardiac, and Diabetic Patients with COVID-19 for Six Months in Unvaccinated Outpatients

Background: This study presents a unique investigation into the relationship between the persistence of IgG antibody levels and reinfection in recovered coronavirus disease 2019 (COVID-19) patients. By shedding light on this aspect, we aim to address concerns about the risk of reinfection in unvaccinated patients, offering a fresh perspective in the current COVID-19 research landscape. Objectives: This study takes a novel approach by focusing on the antibody response and reinfection in COVID-19 patients who were treated in outpatient settings for six months. This approach distinguishes our research within the broader context of COVID-19 studies. Methods: Our comprehensive and rigorous prospective cohort study included 149 COVID-19 outpatients referred to Imam Ali Clinic in Dezfoul City, Khuzestan province, Iran. Data was meticulously collected from September 2021 to February 2022. All unvaccinated patients underwent RT-PCR testing, and their anti-SARS-CoV-2 IgM/IgG levels were measured at the onset of illness. Serum IgG levels were then measured again after three and six months using ELISA. Results: All COVID-19 patients had their IgG antibody levels tested three times (on days two to four of the illness, at three months, and at six months). Significant differences in IgG antibody levels were observed between the vaccinated and unvaccinated groups during each period (P < 0.05). Additionally, there were substantial differences between the hypertension and non-hypertension groups (P = 0.032). Importantly, our findings reaffirm the impartiality of our research, as no significant differences were found between reinfection rates and various demographic or disease-related factors. Conclusions: The findings of this study suggest that high levels of IgG antibodies in unvaccinated patients could potentially reduce the risk of reinfection. This insight could have important implications for public health strategies and the management of COVID-19 in unvaccinated populations, providing valuable information for decision-makers in the field.

A cynomolgus monkey E. coli urinary tract infection model confirms efficacy of new FimH vaccine candidates.

The increase in urinary tract infections (UTI) caused by antibiotic-resistant Escherichia coli requires the development of new therapeutic agents and prophylactic vaccines. To evaluate the efficacy of new lead candidates, we implemented a cynomolgus macaque UTI challenge model that mimics human uncomplicated cystitis in response to transurethral challenge with a multidrug-resistant (MDR) E. coli serotype O25b ST131 isolate. E. coli fimbrial adhesin FimH and O-antigens are separately under clinical evaluation by others as vaccine candidates to prevent UTI and invasive urosepsis disease, respectively. Accordingly, we assessed the protective efficacy of three 50-µg intramuscular doses of a novel recombinant FimH antigen adjuvanted with liposomal QS21/MPLA compared with saline placebo in groups of nine animals. A third group was vaccinated with this FimH formulation in combination with 1 µg each of a four-valent mixture of serotype O1a, O2, O6, and O25b O-antigen CRM197 lattice glycoconjugates. Both vaccines elicited high levels of serum FimH IgG and adhesin blocking antibodies at the time of bacterial challenge and, for the combination group, O-antigen-specific antibodies. Following bacterial challenge, both vaccinated groups showed >200- and >700-fold reduction in bacteriuria at day 2 and day 7 post-infection compared with placebo, respectively. In parallel, both vaccines significantly reduced levels of inflammatory biomarkers IL-8 and myeloperoxidase in the urine at day 2 post-infection relative to placebo. Results provide preclinical proof-of-concept for the prevention of an MDR UTI infection by these new vaccine formulations.

Phase II Trial of HER-Vaxx, a B-cell Peptide-Based Vaccine, in HER2-Overexpressing Advanced Gastric Cancer Patients Under Platinum-Based Chemotherapy (HERIZON).

A multicenter, randomized, open-label, phase II study (HERIZON; NCT02795988) was conducted to evaluate the clinical and immunologic efficacy of HER-Vaxx (IMU-131), a B-cell, peptide-based vaccine targeting HER2 overexpressed in 6% to 30% of gastroesophageal adenocarcinomas (GEA). Patients (n = 36) with GEA were treated with standard-of-care chemotherapy (n = 17) or HER-Vaxx plus chemotherapy (n = 19), using the recommended phase 2 dose for the vaccine. Overall survival (OS; primary endpoint), safety, progression-free survival (PFS), clinical response (secondary endpoints), and vaccine-induced HER2-specific antibody levels in serum and correlation with tumor response rates (exploratory endpoints) were investigated. A 40% OS benefit [HR, 0.60; median OS, 13.9 months; 80% confidence interval (CI), 7.52-14.32] for patients treated with HER-Vaxx plus chemotherapy compared with OS of 8.31 months (80% CI, 6.01-9.59) in patients that received chemotherapy alone. A 20% PFS difference was obtained for the vaccination arm (HR, 0.80; 80% CI, 0.47, 1.38). No additional toxicity due to HER-Vaxx was observed. The vaccine-induced high levels of HER2-specific total IgG and IgG1 antibodies (P < 0.001 vs. controls) that significantly correlated with tumor reduction (IgG, P = 0.001; IgG1, P = 0.016), had a significant capacity in inhibiting phosphorylation of the intracellular HER2-signaling pathways, mediated antibody-dependent cellular cytotoxicity, and decreased immunosuppressive FOXP3+ regulatory T cells. HER-Vaxx plus standard chemotherapy exhibits an excellent safety profile and improves OS. Furthermore, vaccine-induced immune response was significantly associated with reduced tumor size compared with standard-of-care chemotherapy. The presented vaccination approach may substitute for treatment with trastuzumab, upon unavailability or toxicity, based on further evidence of equivalent treatment efficacy.

Influenza A Vaccine Candidates Based on Virus-like Particles Formed by Coat Proteins of Single-Stranded RNA Phages Beihai32 and PQ465.

Efficient control of influenza A infection can potentially be achieved through the development of broad-spectrum recombinant vaccines based on conserved antigens. The extracellular domain of the transmembrane protein M2 of influenza A virus (M2e) is highly conserved but poorly immunogenic and needs to be fused to an adjuvant protein or carrier virus-like particles (VLPs) to increase immunogenicity and provide protection against infection. In this study, we obtained VLPs based on capsid proteins (CPs) of single-stranded RNA phages Beihai32 and PQ465 bearing the M2e peptides. Four copies of the M2e peptide were linked to the C-terminus of the CP of phage Beihai32 and to the N and C termini of the CP of phage PQ465. The hybrid proteins, being expressed in Escherichia coli, formed spherical VLPs of about 30 nm in size. Immunogold transmission electron microscopy showed that VLPs formed by the phage PQ465 CP with a C-terminal M2e fusion present the M2e peptide on the surface. Subcutaneous immunization of mice with VLPs formed by both CPs containing four copies of the M2e peptide at the C termini induced high levels of M2e-specific IgG antibodies in serum and provided mice with protection against lethal influenza A virus challenge. In the case of an N-terminal fusion of M2e with the phage PQ465 CP, the immune response against M2e was significantly lower. CPs of phages Beihai32 and PQ465, containing four copies of the M2e peptide at their C termini, can be used to develop recombinant influenza A vaccine.

Characteristics of virus-specific immunological reactions following COVID-19 vaccination in heart transplant recipients

Heart transplant patients are at an increased risk of COVID-19 infection adverse outcomes because of underlying immunosuppression and concomitant comorbidities. To date, all large-scale randomized controlled trials for various COVID-19 vaccines have excluded solid organ transplant recipients. Therefore, the efficacy and safety of coronavirus infection prevention using COVID-19 vaccines in transplant heart patients has not been sufficiently studied. In this research, the evaluation of virus-specific immunological reactions after vaccination (double Vero Cell vaccination and Sputnik Light booster vaccination) in heart transplant patients has been carried out. In vaccinated heart transplant individuals who did not have a history of COVID-19, starting from 4–6 months after the 2nd dose of the vaccine, an increase in antibodies to S protein level of was observed, while maintaining statistically significant differences for 9–12 months after vaccination (regardless of whether with or without booster vaccination). However, the concentration of antibodies remained low, and 37% of patients detected no antibodies. In vaccinated heart transplant individuals following the previous COVID-19 infection, as compared to seronegative patients, post-vaccination immunity is accompanied by maintaining a high level of virus-specific IgG antibodies to the S protein of the SARS-CoV-2 virus in the dynamics of the post-vaccination period with a statistically significant increase of these antibodies by 9–12 months after booster vaccination. The specific cellular response (according to the assessment of CD3⁺154⁺ and CD3⁺IFNγ⁺ TNFα⁺ cells) to the S protein of the SARS-CoV-2 virus remained low throughout the entire follow-up period, was recorded in 5–40% of heart transplant patients and statistically significant changes in the number of spikereactive lymphocytes were observed in patients with a history of COVID-19 by 4–6 months after administration of the 2nd dose of the vaccine. This, together with the results of the assessment of the humoral response, indicates a more pronounced post-vaccination immunity in patients with a hybrid immunity. While developing a methodology for assessing the risk and benefit of a vaccination strategy for individual heart transplant patients, clinical efficacy, ongoing monitoring of rare serious adverse events, and data on vaccine immunogenicity should be taken into account.

Immunogenicity of an Inactivated Senecavirus A Vaccine with a Contemporary Brazilian Strain in Mice.

Senecavirus A (SVA) is a picornavirus that is endemic in swine, causing a vesicular disease clinically indistinguishable from other vesicular diseases, like foot-and-mouth disease. The widespread viral circulation, constant evolution, and economic losses caused to the swine industry emphasize the need for measures to control the agent. In this study, we evaluated the immunogenicity of a whole-virus-inactivated vaccine using a representative contemporary Brazilian SVA strain in Balb/ByJ mice. The animals were vaccinated with two doses by an intramuscular route. The humoral response induced by the vaccination was evaluated by an in-house ELISA assay for IgG detection. The cellular response was assessed by flow cytometry after in vitro SVA stimulation in splenocyte cultures from vaccinated and non-vaccinated groups. Protection against SVA was assessed in the experimental groups following an oral challenge with the homologous virus. The vaccination induced high levels of IgG antibodies and the proliferation of CD45R/B220+sIgM+, CD3e+CD69+, and CD3e+CD4+CD44+CD62L- cells. These results indicate the immunogenicity and safety of the vaccine formulation in a murine model and the induction of humoral and cellular response against SVA.

Fusion expression and immunogenicity of receptor-binding domains of porcine deltacoronavirus and porcine epidemic diarrhea virus

This study aims to develop an effective bivalent subunit vaccine that is promising to prevent both porcine deltacoronavirus (PDCoV) and porcine epidemic diarrhea virus (PEDV). The receptor-binding domains (RBDs) of PDCoV and PEDV were fused and cloned into the eukaryotic expression vector pCDNA3.1(+). The fusion protein PDCoV-RBD-PEDV-RBD (pdRBD-peRBD) was expressed by the ExpiCHOTM expression system and purified. Mice were immunized with the fusion protein at three different doses (10, 20, and 30 μg). The humoral immune response and cellular immune response induced by the fusion protein were evaluated by ELISA and flow cytometry. The neutralization titers of the serum of immunized mice against PDCoV and PEDV were determined by the microneutralization test. The results showed that high levels of IgG antibodies were induced in the three different dose groups after booster immunization, and there was no significant difference in the antibody level between different dose groups, indicating that the immunization dose of 10 μg could achieve the fine immune effect. The results of flow cytometry showed that the immunization groups demonstrated increased proportion of CD3+CD4+ T cells and decreased proportion of CD3+CD8+ T cells, which was consistent with the expectation about the humoral immune response induced by the subunit vaccine. At the same time, the levels of interleukin (IL)-2, IL-4, and interferon (IFN)-γ in the serum were determined. The results showed that the fusion protein induced both humoral immune effect and cellular immune response. The results of the neutralization test showed that the antibody induced by 10 μg fusion protein neutralized both PDCoV and PEDV in vitro, with the titers of 1:179.25 and 1:141.21, respectively. The above results suggested that the pdRBD-peRBD could induce a high level of humoral immune response at a dose of 10 μg, and the induced antibody could neutralize both PDCoV and PEDV. Therefore, the fusion protein pdRBD-peRBD is expected to be an effective subunit vaccine that can simultaneously prevent PDCoV and PEDV.

Autoimmune hepatitis – an increasingly common cause of hypertransaminasaemia among children. Case report and literature review

Autoimmune hepatitis is a chronic inflammatory process of unknown ethology, characterised by high levels of transaminases and IgG antibodies, the presence of tissue autoantibodies, and a typical histological picture. In the population of children, the paediatric form of autoimmune hepatitis and autoimmune sclerosing cholangitis are collectively classified as juvenile autoimmune liver disease. The condition often coexists with other autoimmune disorders. This paper aims to present the clinical profile of a paediatric patient with full-blown autoimmune hepatitis and describe the available therapies. The patient, a 13-year-old boy, was referred to a specialised hospital because of increasing hypertransaminasaemia. The patient was hospitalised for the first time at a district hospital for abdominal pain, and during his stay, elevated transaminases were found with a tendency to increase in follow-up tests. The picture suggested an inflammatory process of the liver and biliary tract. Upper gastrointestinal endoscopy revealed lesions consistent with chronic gastritis and portal gastropathy. Treatment included thiazolidinedioic acid, vitamin K, ursodeoxycholic acid, rifaximin, ciprofloxacin, and proton pump inhibitors. Therapy is aimed at maintaining immunosuppression and inhibiting the inflammatory response that leads to cirrhosis, and most commonly uses steroids alongside proton pump inhibitors for added protection or, alternatively, mycophenolate mofetil, cyclosporine A, tacrolimus, and biologic therapy. Ursodeoxycholic acid also exhibits immunomodulatory properties and makes it possible to reduce steroid doses and thus decrease the likelihood of adverse effects of therapy.

Three SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective

As the new SARS-CoV-2 Omicron variants and subvariants emerge, there is an urgency to develop intranasal, broadly protective vaccines. Here, we developed highly efficacious, intranasal trivalent SARS-CoV-2 vaccine candidates (TVC) based on three components of the MMR vaccine: measles virus (MeV), mumps virus (MuV) Jeryl Lynn (JL1) strain, and MuV JL2 strain. Specifically, MeV, MuV-JL1, and MuV-JL2 vaccine strains, each expressing prefusion spike (preS-6P) from a different variant of concern (VoC), were combined to generate TVCs. Intranasal immunization of IFNAR1−/− mice and female hamsters with TVCs generated high levels of S-specific serum IgG antibodies, broad neutralizing antibodies, and mucosal IgA antibodies as well as tissue-resident memory T cells in the lungs. The immunized female hamsters were protected from challenge with SARS-CoV-2 original WA1, B.1.617.2, and B.1.1.529 strains. The preexisting MeV and MuV immunity does not significantly interfere with the efficacy of TVC. Thus, the trivalent platform is a promising next-generation SARS-CoV-2 vaccine candidate.

Clinical validation of circulating immune complexes for use as a diagnostic marker of canine leishmaniosis.

Canine leishmaniosis (CanL) is a systemic disease that affects dogs. When multiplication of the parasite cannot be controlled, dogs consistently show high levels of antigen and IgG antibodies, which lead to the formation of circulating immune complexes (CIC). Timely intervention to reduce the parasite load and CIC levels is crucial for preventing irreversible organ damage. However, a diagnostic test to quantify CIC levels is currently lacking. In this real-world study, we aimed to examine the performance of a new ELISA to measure CIC levels in dogs naturally infected with Leishmania infantum. Thirty-four dogs were treated according to their clinical condition and followed for 360 days. Before (day 0) and after treatment (days 30, 90, 180, 270, and 360), all dogs underwent a physical examination, and blood samples were obtained for CBC, biochemical profile, serum protein electrophoresis and IFAT. Serum PEG-precipitated CIC were determined by ELISA. Our results indicate higher CIC levels in dogs in advanced disease stages showing higher antibody titres (p < 0.0001, r = 0.735), anemia (p < 0.0001), dysproteinemia (p < 0.0001), and proteinuria (p = 0.004). Importantly, dogs responding well to treatment exhibited declining CIC levels (p < 0.0001), while in poor responders and those experiencing relapses, CIC were consistently elevated. CIC emerged as a robust discriminator of relapse, with an area under the curve (AUC) of 0.808. The optimal cut-off to accurately identify relapse was an optical density of 1.539. Our findings suggest that declining CIC levels should be expected in dogs showing a favorable treatment response. Conversely, in dogs displaying a poor response and recurrent clinical relapses, CIC levels will be high, emphasizing the need for vigilant monitoring. These findings suggest that CIC could serve as a valuable biomarker for disease progression, treatment efficacy, and relapse detection in CanL. Our study contributes to enhancing diagnostic approaches for CanL and underscores the potential of CIC as a complementary tool in veterinary practice. As we move forward, larger studies will be essential to confirm these findings and establish definitive cut-offs for clinical application.

Long-Term Immunological Alertness and Response to COVID-19 Vaccination-Conditions for Prevention in Early Palliative Oncological Care Patients.

Aside from the general population, the COVID-19 pandemic has also affected a group of patients in palliative oncology care. In this study, long-term immune responses against SARS-CoV-2 after vaccination were monitored in a cohort of patients in palliative oncology care. This non-randomized, prospective, and open-label pilot study recruited patients from the Palliative Oncology Program and included 147 patients, of which 80 were females (54.4%) and 67 males (45.6%). The overall evaluation included current health status, SARS-CoV-2 anti-S IgG titer, and neutralizing antibodies using the SARS-CoV-2 virus neutralization test (VNT). Anti-S IgG antibody analysis revealed high (H) antibody levels in 35.7% (n = 10) and very high (VH) levels in 39.3% (n = 11) of patients after the second vaccination dose. Similarly, after the third dose, H was found in 29.6% (n = 32) and VH in 55.5% (n = 60) of patients. High and very high anti-S IgG antibody levels were consistent with high VNT titers (>2560) and H antibody levels in 17.1% (n = 12) or VH in 82.9% (n = 58) of patients. Patients with two or more doses showed H and VH antibody levels at a median of 451 and 342 days after vaccination, respectively. In this clinical trial, patients showed high and very high levels of anti-S IgG antibodies over a longer period of time. These patients did not show reduced immunological responses to the COVID-19 vaccine challenge. We can assume that prevention through vaccination can reduce the risk of complications or death from COVID-19 in patients in early palliative oncology care.

Analysis of the Presence and Levels of IgG Antibodies Directed against the S1 Protein Receptor Binding Domain and the N Protein of SARS-CoV-2 in Patients with Multiple Sclerosis Treated with Immunomodulatory Therapies.

The coronavirus 2019 disease (COVID-19) course and serological statuses of patients with relapsing-remitting multiple sclerosis (RRMS), treated with disease-modifying therapies (DMTs) are generally parallel that of the general population. Over the pandemic's course, however, a notable increase in the number of RRMS patients who received vaccination against severe acute respiratory coronavirus 2 (SARS-CoV-2) and those who had COVID-19 (symptomatic and asymptomatic) was reported. This virus and/or vaccination likely influenced DMT-treated RRMS patients' serological statuses regarding the presence of SARS-CoV-2 antibodies and their quantitative expression. This investigation assesses the presence and levels of the antibody directed against the S1 protein receptor binding domain (SRBD) and against the N protein of SARS-CoV-2 in 38 DMT-treated RRMS patients. The findings indicate that people vaccinated against SARS-CoV-2 exhibited significantly higher levels of IgG antibodies against S1-RBD at both assessment points. Patients with a prior history of COVID-19 demonstrated statistically significant increases in anti-N antibodies at visit 1, whereas such statistical significance was not observed at visit 2. DMT-treated RRMS patients generated neutralizing antibodies following vaccination and/or COVID-19 infection. Nevertheless, it is noteworthy that antibody levels more accurately reflect the serological status and exhibit a stronger correlation with vaccination than just the presence of antibodies.

A subunit-based influenza/SARS-CoV-2 Omicron combined vaccine induced potent protective immunity in BALB/c mice.

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

CRISPR/Cas9-edited duck enteritis virus expressing Pmp17G of Chlamydia psittaci induced protective immunity in ducklings.

Chlamydia psittaci is threatening to the animal industry and human beings. Live attenuated duck enteritis virus (DEV) is considered a good vaccine vector. In the present study, the Pmp17G antigen of C. psittaci was expressed in DEV to construct a recombinant DEV-Pmp17G vaccine. The growing curve of the rDEV-Pmp17G vaccine was comparable to the parental DEV strain, and Pmp17G protein expression was detected in the cytosol and membrane of the infected host cells. A total of 30 ducklings assigned to 5 groups were used to evaluate the vaccine efficacy. The birds in the vaccine groups received 15 000 plaque forming units of the rDEV-Pmp17G vaccine via hypodermic injection. In contrast, the control groups received intramuscular inoculation with 1×103 embryo lethal dose of DEV vector or 50µg of commercial recombinant major outer membrane protein (MOMP) vaccine. The rDEV-Pmp17G vaccine induced significantly higher levels of IgG antibodies than the commercial MOMP did on day 14, and the IgG antibodies persisted for 28 days. Moreover, the rDEV-Pmp17G vaccine also induced higher levels of lymphocyte proliferations compared to the DEV vector. The vaccinated animals significantly reduced lesions and enhanced bacterial clearance in the lungs and throats compared to the MOMP immunization. Thus, the rDEV-Pmp17G vaccine induced persistent IgG antibodies and lymphocyte proliferation against C. psittaci infection.

Synthesis and evaluation of gold nanoparticles conjugated with five antigenic peptides derived from the spike protein of SARS-CoV-2 for vaccine development

Introduction: The development of innovative anti-COVID-19 vaccines is a need to ensure the population’s immunity worldwide, with broad protection against variants of concern and low cost as the main goals. Gold nanocarriers are potential entities that could aid in the development of innovative vaccines having thermal stability, high immunogenicity, and safety as the main attributes. Moreover, this approach could lead to adjuvant-free formulations, which will reduce the costs of vaccines.Methods: In this study, five peptides (P1, P2, P3, P4, and P5) corresponding to linear epitopes of the SARS-CoV-2 spike (S) protein were chemisorbed on gold nanoparticles (AuNP) of 20 nm, prefunctionalized with heterobifunctional polyethylene glycol, by using glutaraldehyde as crosslinker to generate nanovaccine prototypes.Results and discussion: The surface modification was confirmed by DLS with an increase of 31.7 ± 1.8 nm in the hydrodynamic diameter and an average ζ potential of −8.3 ± 2.2 mV in PBS (as excipient). The coupling concentration achieved was 23.7 ± 7.1 μg of peptide per mg AuNP. These AuNP-based conjugates showed no inherent toxicity in assays performed with HEK293T cells, in which a 100–1,000 μg/mL concentration range only led to a temporary decrease of up to 30% in cell viability after 48 h of treatment with restoration by 72 h. The immunogenicity of the conjugates produced was assessed in test mice subjected to three subcutaneous doses at 2-week intervals. Significant levels of IgM against each target peptide were observed at an early stage of the immunization scheme in all groups, reaching maximum levels after the second dose, whereas the IgG response increased after the third dose. The AuNP-P2, AuNP-P3, and AuNP-P5 conjugates induced the highest levels of IgG antibodies, lasting for at least 2 months after the last boost, with a predominance of the IgG1 subclass. Although the magnitude of the response induced by the gold conjugates was comparable to that with alum as adjuvant, these nanoconjugates induced a longer response. Our data support the use of AuNP as carriers in innovative vaccines against SARS-CoV-2.

Post Covid-19 Effect on Avascular Necrosis of Hip Joint

Background and objectives: The exact course of Severe acute respiratory syndrome (SARS) -2(COVID-19) and itscomplications on multiorgan system are complex and still under studies. Musculoskeletal system has also beenaffected post covid in various forms. This study was taken up to analyse the effects of covid-19 disease on the hipbone and join tissue.Materials and Methods: Retrospective analysis of ten patients was done who had been hospitalised with covid-19infection and later complained of hip pain . They underwent MR imaging and were found to have degenerativechanges characterizing with avascular necrosis (AVN) of head of femur .One of them had history of previoussurgery of femur with PFN, doing well but developed AVN after COVID .Results: Observation of this group showed a clear correlation among the history of COVID-19 disease in thepatients, moderately severe symptoms, high levels of IgG antibodies, and the time of occurrence of joint changes.No other risk factors for AVN or autoimmune or degenerative diseases were found in the study group. The groupof patients responded well to empirical treatment with anti-inflammatory drugs ans supportive therapy, whichsubsided acute inflammatory symptoms and pain in the joints.Conclusions: It is concluded that there have been obvious musculoskeletal complications in covid patientsincluding AVN which could be attributed to the high use steroids and microembolism leading to bone necrosis.Hence more studies and long follow-up is suggested.

Post Covid-19 Effect on Avascular Necrosis of Hip Joint

Background and objectives: The exact course of Severe acute respiratory syndrome (SARS) -2(COVID-19) and itscomplications on multiorgan system are complex and still under studies. Musculoskeletal system has also beenaffected post covid in various forms. This study was taken up to analyse the effects of covid-19 disease on the hipbone and join tissue.Materials and Methods: Retrospective analysis of ten patients was done who had been hospitalised with covid-19infection and later complained of hip pain . They underwent MR imaging and were found to have degenerativechanges characterizing with avascular necrosis (AVN) of head of femur .One of them had history of previoussurgery of femur with PFN, doing well but developed AVN after COVID .Results: Observation of this group showed a clear correlation among the history of COVID-19 disease in thepatients, moderately severe symptoms, high levels of IgG antibodies, and the time of occurrence of joint changes.No other risk factors for AVN or autoimmune or degenerative diseases were found in the study group. The groupof patients responded well to empirical treatment with anti-inflammatory drugs ans supportive therapy, whichsubsided acute inflammatory symptoms and pain in the joints.Conclusions: It is concluded that there have been obvious musculoskeletal complications in covid patientsincluding AVN which could be attributed to the high use steroids and microembolism leading to bone necrosis.Hence more studies and long follow-up is suggested.

Development of an RBD-Fc fusion vaccine for COVID-19

Although the global pandemic of SARS-CoV-2 has passed, there are still regional outbreaks that continue to jeopardize human health. Hence, there is still a great deal of interest in developing an efficient vaccine that can quickly and effectively prevent reemerging outbreaks of SARS-CoV-2. Delta variant was once a dominant strain in the world in 2021, and we first constructed a recombinant RBDdelta-Fc fusion vaccine by coupling the RBD of Delta variant with the human Fc fragment. This Fc fusion strategy increases the immunogenicity of the recombinant RBD vaccine, with a long-lasting high level of IgG antibodies and neutralizing antibodies induced by RBDdelta-Fc vaccine. This RBDdelta-Fc vaccine, as well as the RBD-Fc vaccine prepared in our previously study, could trigger a durable immune effect by the heterologous boosting immunity, and the RBD-Fc induced a quicker humoral immune response than the homologous immunization with inactivated vaccines. In conclusion, the Fc fusion strategy has a significant role in enhancing the immunogenicity of recombinant protein vaccines, thus promising the development of a safe and efficient vaccine for the heterologous boosting against SARS-CoV-2.

Enhancing Protective Antibodies against Opioids through Antigen Display on Virus-like Particles.

Opioid use disorder (OUD) has become a public health crisis, with recent significant increases in the number of deaths due to overdose. Vaccination can provide an attractive complementary strategy to combat OUD. A key for high vaccine efficacy is the induction of high levels of antibodies specific to the drug of abuse. Herein, a powerful immunogenic carrier, virus-like particle mutant bacteriophage Qβ (mQβ), has been investigated as a carrier of a small molecule hapten 6-AmHap mimicking heroin. The mQβ-6-AmHap conjugate was able to induce significantly higher levels of IgG antibodies against 6-AmHap than mice immunized with the corresponding tetanus toxoid-6-AmHap conjugate in head-to-head comparison studies in multiple strains of mice. The IgG antibody responses were persistent with high anti-6-AmHap titers 600 days after being immunized with mQβ-6-AmHap. The antibodies induced exhibited strong binding toward multiple heroin/morphine derivatives that have the potential to be abused, while binding weakly to medications used for OUD treatment and pain relief. Furthermore, vaccination effectively reduced the impacts of morphine on mice in both ambulation and antinociception assays, highlighting the translational potential of the mQβ-6-AmHap conjugate to mitigate the harmful effects of drugs of abuse.