Increase In Antibody Titer Research Articles

Outer membrane vesicles (OMVs) from Tenacibaculum maritimum as a potential vaccine against fish tenacibaculosis

Outer membrane vesicles (OMVs) have been gained increasing attention in vaccinology due to their ability to induce strong protective humoral and cell-mediated immunity. The Gram-negative bacterium Tenacibaculum maritimum, the causative agent of marine tenacibaculosis, poses a significant challenge to the global aquaculture industry due to its difficult prophylaxis. In previous studies, we demonstrated that OMV production is a key virulence mechanism in T. maritimum. Building on this, the present study aimed to evaluate the efficacy of a natural, encapsulated multi-antigen vaccine made from adjuvant-free, crude T. maritimum OMVs (Tm-OMVs). A vaccination experiment using SP9.1-OMVs was conducted in juvenile turbot (Scophthalmus maximus L.), followed by a T. maritimum bath challenge. Immune responses in the turbot were assessed by measuring anti-Tm antibody levels and analyzing the expression of eight key immune-related genes (il-1β, il-8, il-22, pcna, c3, cd4-1, ifng2, cd8α). The results showed that immunization with SP9.1-OMVs provided significant protection against T. maritimum infection (RPS = 70 %). Vaccinated fish exhibited a dose-dependent increase in anti-Tm antibody titers in blood plasma, along with rapid induction of both innate (il-1β, il-8, il-22, c3) and adaptive (cd4-1, ifng2, cd8α) immune genes as early as 4 h post-bath challenge. These findings offer new insights into the early immune response of turbot following T. maritimum infection and could serve as a foundation for developing novel OMV-based vaccines.

Continuous Treatment with IncobotulinumtoxinA Despite Presence of BoNT/A Neutralizing Antibodies: Immunological Hypothesis and a Case Report.

Botulinum Neurotoxin A (BoNT/A) is a bacterial protein that has proven to be a valuable pharmaceutical in therapeutic indications and aesthetic medicine. One major concern is the formation of neutralizing antibodies (nAbs) to the core BoNT/A protein. These can interfere with the therapy, resulting in partial or complete antibody (Ab)-mediated secondary non-response (SNR) or immunoresistance. If titers of nAbs reach a level high enough that all injected BoNT/A molecules are neutralized, immunoresistance occurs. Studies have shown that continuation of treatment of neurology patients who had developed Ab-mediated partial SNR against complexing protein-containing (CPC-) BoNT/A was in some cases successful if patients were switched to complexing protein-free (CPF-) incobotulinumtoxinA (INCO). This seems to contradict the layperson's basic immunological understanding that repeated injection with the same antigen BoNT/A should lead to an increase in antigen-specific antibody titers. As such, we strive to explain how immunological memory works in general, and based on this, we propose a working hypothesis for this paradoxical phenomenon observed in some, but not all, neurology patients with immunoresistance. A critical factor is the presence of potentially immune-stimulatory components in CPC-BoNT/A products that can act as immunologic adjuvants and activate not only naïve, but also memory B lymphocyte responses. Furthermore, we propose that continuous injection of a BoN/TA formulation with low immunogenicity, e.g., INCO, may be a viable option for aesthetic patients with existing nAbs. These concepts are supported by a real-world case example of a patient with immunoresistance whose nAb levels declined with corresponding resumption of clinical response despite regular INCO injections.

Monitoring of Leishmania infantum in captive non-human primates in Spain

Cases of Leishmania infantum infection have recently been reported in non-human primates (NHPs) in Spain causing severe clinical disease in critically endangered orangutans (Pongo pygmaeus pygmaeus). The aim of this study was to determine exposure and risk factors associated with L. infantum infection in NHPs housed in zoos and wildlife rescue centers (WRC) in Spain. Between 2007 and 2023, sera from 252 NHPs belonging to 47 different species were collected at 15 centers. Indirect immunofluorescence was used to detect the presence of antibodies against L. infantum (cut-off ≥1:80). In addition, hair samples from 78 individuals were tested for Leishmania kDNA by real-time quantitative PCR (qPCR). Anti-Leishmania antibodies were detected in 4.0 % (10/252; 95 %CI: 1.6–6.4) of the NHPs tested at 26.7 % (4/15) of the centers sampled. Twenty-two NHPs were longitudinally sampled between 2010 and 2023: one ring-tailed lemur (Lemur catta) seroconverted and a seropositive orangutan increased antibody titers during the study period. Leishmania infantum kDNA was found in 62.8 % (49/78; 95 %CI: 52.1–73.6) of animals and at all centers sampled (100 %; 7/7). Phylogenetic analysis revealed high homology between the sequence obtained and strains previously isolated in humans, dogs and captive and free-living wildlife species in Spain. To the authors´ knowledge, this is the first report of Leishmania kDNA detection in NHP hair samples. The results indicate that hair samples could be a useful, non-invasive method of detection of L. infantum infection in these species. This is also the first large-scale survey of L. infantum conducted in NHP species in Europe. We report for the first time the presence of Leishmania kDNA in nine different NHP species belonging to the families Cercopithecidae, Lemuridae, and Hylobatidae, expanding the host range for this parasite. The main risk factors associated with L. infantum infection were: age (≥5 years old) and body size (large). Our results demonstrate widespread circulation of this parasite among NHPs housed in Spain, which could be of conservation and public health concern. Monitoring and control programs should be implemented in zoos and WRCs to minimize the risk of NHP exposure to L. infantum in endemic areas worldwide.

A novel dual-epigenetic inhibitor enhances recombinant monoclonal antibody expression in CHO cells

Epigenetic regulation plays a central role in the regulation of a number of cellular processes such as proliferation, differentiation, cell cycle, and apoptosis. In particular, small molecule epigenetic modulators are key elements that can effectively influence gene expression by precisely regulating the epigenetic state of cells. To identify useful small-molecule regulators that enhance the expression of recombinant proteins in Chinese hamster ovary (CHO) cells, we examined a novel dual-HDAC/LSD1 inhibitor I-4 as a supplement for recombinant CHO cells. Treatment with 2 μM I-4 was most effective in increasing monoclonal antibody production. Despite cell cycle arrest at the G1/G0 phase, which inhibits cell growth, the addition of the inhibitor at 2 µM to monoclonal antibody-expressing CHO cell cultures resulted in a 1.94-fold increase in the maximal monoclonal antibody titer and a 2.43-fold increase in specific monoclonal antibody production. In addition, I-4 significantly increased the messenger RNA levels of the monoclonal antibody and histone H3 acetylation and methylation levels. We also investigated the effect on HDAC-related isoforms and found that interference with the HDAC5 gene increased the monoclonal antibody titer by 1.64-fold. The results of this work provide an effective method of using epigenetic regulatory strategies to enhance the expression of recombinant proteins in CHO cells.Key points• HDAC/LSD1 dual-target small molecule inhibitor can increase the expression level of recombinant monoclonal antibodies in CHO cells.• By affecting the acetylation and methylation levels of histones in CHO cells and downregulating HDAC5, the production of recombinant monoclonal antibodies increased.• It provides an effective pathway for applying epigenetic regulation strategies to enhance the expression of recombinant proteins.

A Preliminary Study to Evaluate the Immune Response to a Booster Dose of the Adult Tetanus-Diphtheria Vaccine (Td) Available in Iran

Background: Despite the availability of tetanus-diphtheria (TD) vaccines in Iran, the seroconversion rate of these products as a booster dose is unknown. Objectives: This study evaluates the seroconversion rate of the Iranian Td vaccine in adults who have not been vaccinated in the past decade. Methods: In this study, 20 adult volunteers aged 18 to 60 who had not received the Td vaccine in the past decade received a booster dose of the Iranian Td vaccine. Twenty-eight days after vaccination, the seroconversion rate was evaluated using the ELISA method. Vaccine adverse events were monitored at three time points after vaccination. Results: Seroconversion rates with the Iranian Td vaccine boosters were 75% and 90%, respectively, based on a 4-fold increase in anti-tetanus toxoid antibody titers and a 2- and 4-fold combination. Significant associations were found between the demographic data, specifically female gender and age 43 years and older, with seroconversion rates. Injection-site pain was the most common adverse reaction, with a frequency of 35%. No adverse events were reported between one week and one month after vaccination. Conclusions: Results showed that a booster dose of the Iranian Td vaccine produced a protective titer (> 0.1 IU/mL) and a long-term protective titer (> 1.0 IU/mL) in 100% of participants. The seroconversion rate of the Iranian Td vaccine was comparable to other common tetanus vaccines, including Tenivac®, Adacel®, Infanrix®, Tetavax®, and Vacteta®. The proportion of suitable candidates for plasma donation, based on minimum (2 IU/mL) and maximum (10 IU/mL) anti-tetanus toxoid antibody titers, was 100% and 45%, respectively.

Interim safety and immunogenicity analysis of the EuCorVac-19 COVID-19 vaccine in a Phase 3 randomized, observer-blind, immunobridging trial in the Philippines.

EuCorVac-19 (ECV-19) is a recombinant receptor binding domain (RBD) COVID-19 vaccine that displays the RBD (derived from the SARS-CoV-2 Wuhan strain) on immunogenic liposomes. This study compares the safety and immunogenicity of ECV-19 to the COVISHIELDTM (CS) adenoviral-vectored vaccine. Interim analysis is presented of a randomized, observer-blind, immunobridging Phase 3 trial in the Philippines in 2600 subjects, with treatment and biospecimen collection between October 2022 and January 2023. Healthy male and female adults who received investigational vaccines were 18 years and older, and randomly assigned to ECV-19 (n = 2004) or CS (n = 596) groups. Immunization followed a two-injection, intramuscular regimen with 4 weeks between prime and boost vaccination. Safety endpoints were assessed in all participants and immunogenicity analysis was carried out in a subset (n = 585 in ECV-19 and n = 290 in CS groups). The primary immunological endpoints were superiority of neutralizing antibody response, as well as noninferiority in seroresponse rate (defined as a 4-fold increase in RBD antibody titers from baseline). After prime vaccination, ECV-19 had a lower incidence of local solicited adverse events (AEs) (12.0% vs. 15.8%, p < 0.01), and solicited systemic AEs (13.1 vs. 17.4%, p < 0.01) relative to CS. After the second injection, both ECV-19 and CS had lower overall solicited AEs (7.8% vs. 7.6%). For immunological assessment, 98% of participants had prior COVID-19 exposure (based on the presence of anti-nucleocapsid antibodies) at the time of the initial immunization, without differing baseline antibody levels or microneutralization (MN) titers against the Wuhan strain in the two groups. After prime vaccination, ECV-19 induced higher anti-RBD IgG relative to CS (1,464 vs. 355 BAU/mL, p < 0.001) and higher neutralizing antibody response (1,303 vs. 494 MN titer, p < 0.001). After boost vaccination, ECV-19 and CS maintained those levels of anti-RBD IgG (1367 vs. 344 BAU/mL, p < 0.001) and neutralizing antibodies (1128 vs. 469 MN titer, p < 0.001). ECV-19 also elicited antibodies that better neutralized the Omicron variant, compared to CS (763 vs. 373 MN titer, p < 0.001). Women displayed higher responses to both vaccines than men. The ECV-19 group had a greater seroresponse rate compared to CS (83% vs. 30%, p < 0.001). In summary, both ECV-19 and CS had favorable safety profiles, with ECV-19 showing diminished local and systemic solicited AE after prime immunization. ECV-19 had significantly greater immunogenicity in terms of anti-RBD IgG, neutralizing antibodies, and seroresponse rate. These data establish a relatively favorable safety and immunogenicity profile for ECV-19. The trial is registered on ClinicalTrials.gov (NCT05572879).

Immunogenicity and Protective Efficacy of an Acellular Pertussis Vaccine Candidate in a Mice Model.

Acellular pertussis vaccines (aPVs) have been developed as an alternative to whole-cell pertussis vaccines (wPVs) due to their similar efficacy but reduced reactogenicity. The aPV contains three or more immunogenic components of BP. We aimed to evaluate the immunogenicity and protective potency of an aPV vaccine produced in our laboratory consisting of pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) in mice. The aPV components were produced and purified from the supernatant and pellet of the bacterial culture. Two doses of formulated vaccine in parallel with two commercial vaccines, were administered intraperitoneally (IP) in mice at 3-week intervals. Antibody titers against aPV antigens were measured by ELISA after primary and booster vaccinations. To assess the protective efficacy, an intranasal challenge with a live pathogenic BP strain was conducted two weeks after the booster vaccination, and bacterial count (colony-forming unit, CFU) in the lungs was conducted two hours and ten days after the challenge. The results demonstrated a significant increase in antibody titers against all pertussis antigens in the serum of vaccinated groups compared to the negative control group, following both the primary and booster doses. No significant differences were observed between our formulation and the commercial vaccines. Furthermore, the CFU results showed complete eradication of infection 10 days after the challenge in all immunized groups, in contrast to the control group. Our aPV formulation, the first aPV candidate developed in Iran, exhibits immunogenicity and protective efficacy comparable to commercial vaccines. Further investigation in human subjects is warranted.

A randomized study to evaluate the safety and immunogenicity of a pentavalent meningococcal vaccine

A randomized, active-controlled, double-blind, first-in-human, phase 1 study was conducted in healthy Korean adults to evaluate the safety, tolerability, and immunogenicity of EuNmCV-5, a new pentavalent meningococcal vaccine targeting serogroups A, C, W, X, and Y. Sixty participants randomly received a single dose of either EuNmCV-5 or MenACWY-CRM, a quadrivalent vaccine containing serogroups A, C, W, and Y. Safety was assessed through monitoring anaphylactic reactions, adverse events for 28 days, and serious adverse events over 180 days. Immunogenicity was assessed via rabbit complement-dependent serum bactericidal antibody (rSBA) assay. EuNmCV-5 was safe, well-tolerated, and elicited a substantial antibody titer increase. The seroprotection rates exceeded 96.7%, and the seroconversion rates were over 85% for all the targeted serogroups. It showed higher seroconversion rates against serogroups A and C (p = 0.0016 and 0.0237, respectively) and elicited a substantial increase in GMT for all targeted serogroups compared to the MenACWY-CRM.ClinicalTrials.gov identifier: NCT05739292.

COVID-19 Vaccine in Lung and Liver Transplant Recipients Exceeds Expectations: An Italian Real-Life Experience on Immunogenicity and Clinical Efficacy of BNT162b2 Vaccine.

This study assessed humoral and T cell-mediated immune responses to the BNT162b2 vaccine in orthotopic liver transplant (OLT) and lung transplant (LUT) recipients who received three doses of the vaccine from March 2021 at our institution. Serum samples were collected 60days post-second and third dose to quantify antibodies against the spike region of SARS-CoV-2 while whole blood samples were collected to analyze the SARS-CoV-2-specific T-cell response using an IFN-γ ELISpot assay. We enrolled 244 OLT and 120 LUT recipients. The third dose increased antibody titres in OLT recipients (from a median value of 131 after the second dose to 5523 IU/mL, p < 0.001) and LUT recipients (from 14.8 to 1729 IU/mL, p < 0.001). T-cell response also increased in OLT recipients (from 8.5 to 23 IFN-γ SFU per 250,000 PBMC, p < 0.001) and LUT recipients (from 8 to 15 IFN-γ SFU per 250,000 PBMC, p < 0.001). A total of 128 breakthrough infections were observed: two (0.8%) OLT recipients were hospitalized due to COVID-19 and one died (0.4%); among LUT recipients, seven were hospitalized (5.8%) and two patients died (1.7%). In conclusion, the three-dose schedule of the BNT162b2 vaccine elicited both humoral and T cell-mediated responses in solid organ transplant recipients. The risk of severe COVID-19 post-vaccination was low in this population.

Immunogenicity, reactogenicity, and safety of a second booster with BNT162b2 or full-dose mRNA-1273: A randomized VACCELERATE trial in adults aged ≥75 years (EU-COVAT-1-AGED Part B)

ObjectivesTo assess the safety and immunogenicity of a fourth vaccination (second booster) in individuals aged ≥75 years. MethodsParticipants were randomized to BNT162b2 (Comirnaty, 30 µg) or messenger RNA (mRNA)-1273 (Spikevax, 100 µg). The primary end point was the rate of two-fold antibody titer increase 14 days after vaccination, targeting the receptor binding domain (RBD) region of wild-type SARS-CoV-2. The secondary end points included changes in neutralizing activity against wild-type and 25 variants. Safety was assessed by monitoring solicited adverse events (AEs) for 7 days. ResultsA total of 269 participants (mean age 81 years, mRNA-1273 n = 135/BNT162b2 n = 134) were included. Two-fold anti-RBD immunoglobulin (Ig) G titer increase was achieved by 101 of 129 (78%) and 116 of 133 (87%) subjects in the BNT162b2 and the mRNA-1273 group, respectively (P = 0.054). A second booster of mRNA-1273 provided higher anti-RBD IgG geometric mean titer: 21.326 IU/mL (95% confidence interval: 18.235-24.940) vs BNT162b2: 15.181 IU/mL (95% confidence interval: 13.172-17.497). A higher neutralizing activity was noted for the mRNA-1273 group. The most frequent AE was pain at the injection site (51% in mRNA-1273 and 48% in BNT162b2). Participants in the mRNA-1273 group had less vaccine-related AEs (30% vs 39%). ConclusionsA second booster of either BNT162b2 or mRNA-1273 provided substantial IgG increase. Full-dose mRNA-1273 provided higher IgG levels and neutralizing capacity against SARS-CoV-2, with similar safety profile for subjects of advanced age.

Immune reactivity of two biological models to vaccination with inactivated vaccine QazVac against coronavirus infection COVID-19.

Specific prevention of a number of infectious diseases has been introduced into the vaccination schedule. The production of immunoprophylactic drugs, in order to establish standard properties, including safety and specific effectiveness, requires strict adherence to manufacturing regulations, and the reliability of the results obtained requires monitoring of these parameters. The specific effectiveness of vaccine preparations is standardized according to the indicators of stimulation of specific antibody response formed in the body of vaccinated model biological objects. Determination of the immune reactivity of white mice to vaccination with the QazVac vaccine to establish the possibility of using them as a biological model in assessing the immunogenicity of the vaccine instead of Syrian hamsters. The immune reactivity of model animals was assessed by the seroconversion rate, dynamics of antibody titers to the SARS-CoV-2 virus formed in the body after vaccination with the test vaccine. In the case of seropositivity of animals before administration of vaccine or placebo, the level of immune reactivity was calculated by the difference in antibody titers between control and vaccinated animals or by the difference in antibody titers before and after immunization. Specific antibodies were detected and their titer was determined using a neutralization reaction. The research results showed that the tested biological models had approximately the same immune reactivity to the administration of the QazVac vaccine, confirmed by the level and dynamics of antibody titers. When analyzing the fold increase in antibody titers in comparison to those of control animals, Syrian hamsters were more reactive compared to mice. But SPF white mice were standardized in their lack of the immune reactivity to SARS-CoV-2 virus before the immunization. The data obtained indicate that the immune reactivity of white mice to the administration of the QazVac vaccine in terms of the rate and dynamics of the formation of virus-neutralizing antibodies is approximately equivalent to the immune reactivity of Syrian hamsters. Before immunization with the vaccine, SPF white mice, in contrast to Syrian hamsters, do not have humoral immunity specific to the SARS-CoV-2 virus. The immune reactivity equivalent to that observed of Syrian hamsters and the absence of antibodies to the SARS-CoV-2 virus at a baseline indicate the superiority of the use of white mice in assessing the immunogenicity of vaccines against COVID-19 and/or obtaining specific factors of humoral immunity.

Donor vs. Donor or Recipient vs. Recipient? A Singular Case of Post Hematopoietic Stem Cell Transplantation Autoimmune Hemolytic Anemia in a Pediatric Patient

Hematopoietic Stem Cell Transplantation (HSCT) is a curative treatment for certain blood disorders, but can lead to complications such as Autoimmune Cytopenia (AIC), particularly Autoimmune Hemolytic Anemia (AIHA). AIHA after HSCT often involves donor-derived antibodies attacking donor red blood cells, but this case report describes a unique case in a 7-year-old male with beta-thalassemia major. Following HSCT, he developed AIHA nine months after transplantation from an unrelated donor. Despite initially successful engraftment, chimerism analysis revealed a decline in donor cells coincident with the onset of AIHA. The patient had severe hemolysis, a positive Direct Coombs Test (DAT) for IgG and C3d, and several antibodies including anti-e, anti- C, and anti-D. Treatment with cyclosporine and prednisone initially stabilized his condition, but discontinuation resulted in relapse, worsening chimerism, and increased antibody titers. Analysis confirmed the predominance of recipient immune cells, suggesting that AIHA was driven by the recipient's immune response against his own red blood cells. This case emphasizes the complexity of immune reconstitution after HSCT and highlights a recipient-versus-recipient mechanism in post-transplant AIHA.

Active immunization with recombinant GnRH6-CRM197 inhibits reproductive function of male rats

Gonadotropin-releasing hormone (GnRH) vaccines have been successfully used for the inhibition of gonadal development and function, but current GnRH-based vaccines often present variability in the response. Cross-reactive material 197 (CRM197) has been used as carrier molecules to enhance an immune response to associated antigens. So, the synthetic mammalian tandem-repeated GnRH hexamer (GnRH6) gene was integrated into the expression plasmid pET-21a. Recombinant GnRH6-CRM197 protein was subsequently overexpressed in Escherichia coli strain BL21 and purified through Nickel column affinity chromatography and the antigenicity and biological effects of GnRH6-CRM197 were evaluated in rats. Sixteen 4-month-old adult male rats were randomly divided into two groups: the GnRH6-CRM197 group (n = 8) and the control group (n = 8). The GnRH6-CRM197 group rats were subcutaneously immunized with 100 μg of GnRH6-CRM197, administered thrice at 2-week intervals with GnRH6-CRM197.The control group received only a white oil adjuvant. Following the initial immunization, the weights of animals were recorded, and blood samples were collected from the orbital sinus at 4, 4.5, 5, 5.5, 6, 6.5, and 7 months. Serum antibody titers and testosterone concentrations were quantified using ELISA and CLIA, respectively. Additionally, testicular tissues were collected for morphological examination. The results revealed a significant increase in serum GnRH antibody titers (p < 0.05), but a significant decrease in serum testosterone concentrations (p < 0.05), and the weight, length, width, and girth of the testis, and the number of spermatogonia cells, spermatocytes, and sperm cells in the immunized rats. Furthermore, seminiferous tubules revealed significant atrophy and no sperm were observed in the immunized animals. Thus, GnRH6-CRM197 may be an effective antigen and a potential immunocastration vaccine.

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Single Vaccination of Ad26.RSV.preF-Based Regimen in Japanese Adults Aged 60 Years and Older.

Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of lower respiratory tract disease (LRTD) in older adults. The Ad26.RSV.preF/RSV preF protein vaccine demonstrated protective efficacy against RSV related LRTD in a Phase 2b study in the United States. Hence, Ad26.RSV.preF/RSV preF protein vaccine candidate was evaluated in the Japanese older adult population. This Phase 1 study evaluated safety, reactogenicity, and immunogenicity of Ad26.RSV.preF/RSV preF protein vaccine at dose level of 1 × 1011 vp/150 μg in Japanese healthy adult aged ≥60 years. The study included a screening Phase, vaccination, 28-day follow up Phase, a 182-day follow-up period, and final visit on Day 183. A total of 36 participants were randomized in a 2:1 ratio to receive Ad26.RSV.preF/RSV preF protein vaccine (n = 24) or placebo (n = 12). After study intervention administration, the safety and immunogenicity analysis were performed as per planned schedule. Immune responses including virus-neutralizing and preF-specific binding antibodies were measured on Days 1, 15, 29, and 183. There were no deaths, SAEs, or AEs leading to discontinuation reported during the study. The Ad26.RSV.preF/RSV preF protein vaccine had acceptable safety and tolerability profile with no safety concern in Japanese older adults. The Ad26.RSV.preF/RSV preF protein vaccine induced RSV-specific humoral immunity, with increase in antibody titers on Days 15 and 29 compared with baseline which was well maintained until Day 183. A single dose of Ad26.RSV.preF/RSV preF protein vaccine had an acceptable safety and tolerability profile and induced RSV-specific humoral immunity in Japanese healthy adults. NCT number: NCT04354480; Clinical Registry number: CR108768.

Serosurveillance of COVID-19 amongst health care workers in a teaching institution - A prospective cohort study in Puducherry district.

The rapid spread and mutation rate of severe acute respiratory syndrome corona virus (SARS-CoV2) demands continuous monitoring in terms of genomic and serosurvival. The current study is designed to track the seroprevalence of health care workers (HCWs) postvaccination, as they may be more susceptible to contracting the SARS-CoV-2 infection compared to the general population. The objective was to identify the seroprevalence rate for SARS-CoV-2 immunoglobulin G (IgG) antibody (N, S1, S2) amongst HCWs of various levels of exposure working in a tertiary care teaching hospital in Puducherry. The present study followed a nonprobability consecutive sampling technique, which involved 216 study participants HCWs from the hospital. IgG antibody levels were measured using EUROIMMUNE Anti SARS-COV-2 ELISA KIT (IG g) ELISA at two points: firstly, 2 weeks after the second dose of vaccination, followed by 2 weeks after the booster dose. Out of the total 216 participants enrolled in the survey, there were 140 males and 76 females, and the maximum number of candidates studied were in the 41-50 age group. Almost 46.7% of the HCWs who participated in the study were seropositive for SARS-CoV-2 in the case of those who were high-risk exposed, while only 30.4% were amongst those who were low-risk exposed. The proportion of study participants who became seropositive increased considerably after the booster dose (65.7%), from 38.0% when tested three months after infection. A significant increase in antibody titres amongst high-risk HCWs postboost vaccination demands continuous monitoring of soluble IgG levels for recommendations of vaccination schedules.

Higher Proinflammatory Cytokines Are Associated With Increased Antibody Titer After a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: Erratum.

Higher Proinflammatory Cytokines Are Associated With Increased Antibody Titer After a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: Erratum.

Effects of Influenza Vaccine on the Immune Responses to SARS-CoV-2 Vaccination.

A number of studies have suggested that influenza vaccination can provide protection against COVID-19, but the underlying mechanisms that could explain this association are still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. A total of 113 participants were enrolled, 74 of whom had no prior COVID-19 diagnosis or significant comorbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARS-CoV-2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARS-CoV-2 vaccinations compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to the influenza vaccine was evaluated, and individuals were stratified as high or low responders. High responders showed increased antibody titers against the SARS-CoV-2 vaccine both after 4 and 12 weeks post-vaccination. Conversely, individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli play a role in the response to the vaccine.

Changes in the avids of IgG antibodies to the S protein of SARS-CoV-2 after coronavirus infection in medical workers of a temporary infections hospital

BACKGROUND: The effector capabilities of humoral immunity are determined not only by the amount of specific antibodies produced in response to an antigenic effect, but also by their qualitative characteristics, which include avidity ― the total strength of binding to the antigen, which determines the duration and effectiveness of post-infectious immunity to SARS-CoV-2.&#x0D; AIM: Is a selective study of the quantity and avidity of IgG antibodies to SARS-CoV-2 over time among medical workers of a temporary infectious diseases hospital in Kazan ― convalescents of COVID-19, during the period from July 2020 to July 2021.&#x0D; MATERIALS AND METHODS: Determination of IgG to the S antigen of SARS-CoV-2 by ELISA was carried out using the test system SARS-CoV-2-IgG quantitative-ELISA-BEST (Vector-Best, Russia) and expressed in BAU/ml (binding antibody units). Antibody avidity was determined using a 4.0 M urea solution and expressed as avidity indices. 1, 4 and 7 months after COVID-19 asymptomatic (n=34); mild severity (n=42); moderate severity (n=29); reinfected (n=34). When statistically processing the data, descriptive statistics methods and the Wilcoxon matched data test were used. Differences were considered significant at p 0.05.&#x0D; RESULTS: IgG avidity to SARS-CoV-2 depended on the severity of COVID-19. The highest rates of avidity indices were found in the group of those who had a moderate form of COVID-19. If in mild and asymptomatic forms there was a parallel decrease in avidity indices and IgG titer, then in moderate forms an increase in antibody titer was accompanied by a decrease in their avidity 4 months after the infection. 7 months after seroconversion, the IgG level decreased almost twofold, both in mild, asymptomatic and moderate forms. In the group of medical workers who had COVID-19 repeatedly, the initially low levels of avidity indices and antibody titers increased in parallel, while avidity indices after 7 months did not decrease, but remained high. Differences in avidity indices determined the subsequent formation of different trends in the development of the humoral immune response, which were mainly characterized by an uneven decrease in IgG and persistence of IgM antibodies for more than 1 month.&#x0D; CONCLUSIONS: The research results expand the understanding of the mechanisms of formation of the humoral immune response and the avidity of IgG antibodies against SARS-CoV-2 in the risk group ― medical workers. The level of humoral immunity decreases in the first six months and varies depending on the severity of COVID-19. The data obtained can be used to identify categories of increased risk of SARS-CoV-2 infection among healthcare workers, make decisions about immunorehabilitation and revaccination against COVID-19.

Post-COVID-19 myocardium and coronary involvement in a young patient: differential diagnosis and comprehensive treatment

The state of the heart after a coronavirus disease 2019 (COVID-19, coronavirus disease 2019) is very diverse and in some cases requires a complex differential diagnosis. We described a 35-year-old smoking male patient who, by the end of the first month after COVID-19, developed left ventricular dysfunction with decrease in ejection fraction to 25-30% and persistent left bundle branch block (LBBB). Echocardiography also detected local contractility disorders. A significant increase in blood anticardiac antibody titers was noted. Myocardial biopsy revealed active lymphocytic myocarditis, coronavirus ribonucleic acid, while coronary angiography revealed extensive stenosis of the anterior interventricular artery. On the first day after balloon angioplasty and stenting, the disappearance of LBBB block was noted with the appearance of deep negative T waves in the precordial leads, which did not allow ruling out a previous myocardial infarction. As a result of treatment of heart failure and steroid therapy, the structural and functional cardiac parameters and the electrocardiography were completely normalized by the end of the second year of treatment. Only a transient LBBB remained at high loads. Cardiac computed tomography after 2 years showed no delayed contrast agent accumulation in the myocardium, and coronary stenosis up to 30%.The mechanisms of complex myocardial and coronary damage (including the role of coronaritis in the atherosclerosis progression) after COVID-19 are discussed.

Abstract CT186: A first-in-human phase 1 dose-escalation and expansion study of intratumoral oncolytic reovirus (RC402) as a monotherapy or in combination with pembrolizumab in advanced solid tumors

Abstract Background: RC402 is an oncolytic reovirus that selectively infects and destroys cancer cells. Preclinical studies have shown that RC402 remodels the tumor immune microenvironments and elicits potent anti-tumor immunity, thereby enhancing immune checkpoint inhibitors. Methods: This Phase I clinical trial (ACTRN12620000777998) was designed to evaluate the safety profiles and antitumor efficacy of intratumoral (IT) RC402 in patients with advanced solid tumors refractory to standard therapy and with accessible tumor lesions for IT injection of RC402. For the dose-escalation part (Phase 1a), the RC402 monotherapy dose was evaluated at 3 dose levels in Part A and the RC402 combination therapy dose with pembrolizumab was evaluated at 2 dose levels in part B using an accelerated titration method followed by a standard 3+3 dose escalation. In the dose-expansion part (Phase 1b), patients were treated with IT RC402 in combination with pembrolizumab at the recommended dose selected from the dose escalation part. RC402 was IT injected on day 1 of each treatment cycle. Fixed-dose pembrolizumab (200mg Q3W) was intravenously administered on day 8 of each treatment cycle for Phase 1a Part B and Phase 1b. Viral shedding was assessed serially in serum, urine, sputum, and stool samples, and neutralizing antibodies to Reovirus Type 3 Dearing were analyzed in serum samples. Results: Nine patients (2 gastric cancer and 1 cutaneous squamous cell carcinoma [cSCC] in Phase 1a Part A, 1 cSCC and 1 colorectal cancer [CRC] in Phase 1a Part B, and 1 cSCC and 3 CRC in Phase 1b) were enrolled and treated with at least two doses of RC402. IT administration of RC402 was generally well tolerated with no dose-limiting toxicities at all dose levels (1.6 × 108, 1.4 × 109, and 1.4 ×1010 PFU) as a monotherapy or in combination with pembrolizumab. The maximum tolerated dose was not reached. There were no treatment-emergent adverse events (TEAEs) leading to treatment discontinuation and no RC402-related serious TEAEs. The most common AEs were chills, fatigue, injection site reactions (erythema and pain) and nausea. Response evaluation showed two complete responses (one patients with cSCC in Phase 1a Part A and another patient with cSCC in the dose expansion part) lasting longer than 90 weeks and 36 weeks, respectively. No viral shedding was detected in any serum, urine, sputum, and stool samples on days 1, 2, and 15 of cycle 1, on day 2 of subsequent cycles and at the end of treatment. All patients showed an initial increase in antireoviral antibody titers on day 1 of cycle 2, followed by a decrease in subsequent cycles. Conclusion: This first-in-human study demonstrated IT RC402 is well tolerated and has a manageable safety profile with preliminary clinical activity as a monotherapy and in combination with pembrolizumab. These results warrant further clinical development of RC402. Citation Format: Mark Voskoboynik, Jia Liu, Ki-Hoon Song, Dong-Guk Park, Min-Hee Ryu, Hong Jae Chon, Chan Kim. A first-in-human phase 1 dose-escalation and expansion study of intratumoral oncolytic reovirus (RC402) as a monotherapy or in combination with pembrolizumab in advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT186.