Increase In Antibody Titer Research Articles

Evaluation of the Effect of Pb Pollution on Avian Influenza Virus-Specific Antibody Production in Black-Headed Gulls (Chroicocephalus ridibundus).

Lead (Pb), an environmental pollutant, has been widely reported to have contaminated mammals, including humans and birds. This study focuses on the effects of Pb pollution on avian influenza virus (AIV) antibody production. A total of 170 black-headed gulls (Chroicocephalus ridibundus) were captured in Tokyo Bay (TBP) from January 2019 to April 2020 and in Mikawa Bay (MBP) from November 2019 to April 2021. The gulls were weighed, subjected to blood sampling, and released with a ring band on their tarsus. The samples were used to measure blood Pb levels (BLL) and AIV-specific antibodies. The BLL were compared using the Wilcoxon two-sample test between the period when black-headed gulls arrived and the wintering period, defined by the number of gulls counted in each area. A significant increase was found in the TBP. A decrease in BLL significantly increased antibody titer during wintering in TBP and MBP. Pb pollution had a negative effect on the production of AIV antibodies. These findings suggest that wild birds that were contaminated by Pb in the environment may facilitate the spread of zoonotic diseases, further increasing the possibility that environmental pollutants may threaten human health.

Effects of ginger extract and/or propolis extract on immune system parameters of vaccinated broilers

Newcastle disease (ND), avian influenza (AI, H5N8), and infectious bronchitis (IB) are important diseases in the poultry industry and cause significant losses. Vaccination isthe most practical method for controlling infectious diseases. To reduce vaccination costs and several disorders in poultry farms, using herbal water supplements for immunomodulation with vaccination is critical to improving or preventing some conditions in the poultry industry. However, drinking water supplementation of ginger extract (GE)/propolis extract (PE) alone/in combination may increase broilers' humoral and cellular immunity due to the immunomodulatory effects of ginger and propolis. This protocol aimed to see how GE/PE alone or in combination improved the immunity, immune organ gene expression, and histology of the immune organs of broilers for 35 d after vaccination against NDV, H5N8, IBV, and IBDV. The chicks were dispensed into 5 groups according to GE and/or PE with vaccination. The control group was offered normal drinking water without any supplements or vaccinations. The GE group was supplemented with ginger extract (1 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The GE+PE group was supplemented with GE (0.5 mL/L drinking water) and PE (0.5 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The PE group was supplemented with propolis extract (1 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The fifth group was the vaccinated untreated group. This experiment showed the immunomodulatory properties of GE and/or PE against 3 common diseases, NDV, AI, and IB, in broiler chicken farms for 35 d applied to a vaccination program. Thus, ginger extract and propolis extract supplementation in drinking water increased antibody titer, INF, IL10, and IL2 and TLR3 gene expression in the bursa of Fabricius, thymus, and spleen, respectively, as well as cellular immunity as indicated by increased CD3, CD4, and CD8 in the bursa of Fabricius, thymus, and spleen, respectively, with normal lymphocytes in the medulla of the bursa, thymus, and spleen. In conclusion, propolis extracts alone or with GE improved all of the metrics mentioned above without harming the histology of the immune organs.

An attenuated strain of cyprinid herpesvirus 2 as a vaccine candidate against herpesviral hematopoietic necrosis disease in gibel carp, Carassius auratus gibelio.

Herpesviral hematopoietic necrosis disease causes by cyprinid herpesvirus 2 (CyHV-2) infection is a high mortality disease that leads to great economic damage to gibel carp, Carassius auratus gibelio aquaculture. In this study, an attenuated strain of CyHV-2 G-RP7 was achieved by subculture on RyuF-2cells derived from the fin of Ryukin-variety goldfish and GiCF cells derived from fin of gibel carp. As the attenuated vaccine candidate, there are no clinical symptoms of gibel carp that immersion or intraperitoneal injection with G-RP7 strain. The protection rates of G-PR7 to gibel carp by immersion and intraperitoneal injection were 92% and 100%, respectively. In the test for virulence reversion, the candidate was propagated through gibel carp six times by intraperitoneal injection with kidney and spleen homogenate of the inoculated fish. During in vivo passages in gibel carp, no abnormality and mortality of the inoculated fish were observed, and the virus DNA copies maintain a low level from the first passage to the sixth passage. The dynamic of virus DNA in each tissue of G-RP7 vaccination fish increased within 1, 3, and 5 days post-immunization, and subsequently decreased and stabilized within 7 and 14 days. In addition, the increase of anti-virus antibody titer was detected both immersion and injection immunization fish 21 days after vaccination by ELISA. These results demonstrated that G-RP7 can be a promising live attenuated vaccine candidate against the disease.

Immunological imprinting of humoral immunity to SARS-CoV-2 in children

Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.

Study of Synergistic Effects of Herbal Meniran (Phyllanthus Niruri L) and Sambiloto (Andrographis Paniculata) as A Substitute Commercial Additive Feed to Improve Immunity Response and Free Chicken Egg Production

This study aims to look at the immune response and egg production of free-range chickens after ND vaccination by administering meniran and Sambiloto extracts. The design used was a completely randomized design. Data on egg production were analyzed using analysis of variance and data on antibody and lymphocyte titers were analyzed descriptively. The results showed that on D+7 after vaccination, there was an increase in ND antibody and lymphocyte titers and in vaccinated chickens the ND titer was in a protective condition (≥log26), whereas in non-vaccinated chickens, the ND titer and lymphocyte levels were in a less protective condition. On H+28 after the vaccine only the vaccine treatment showed a protective condition, but the administration of meniran and Sambilotol extracts was able to maintain the titer rate longer than without giving Meniran and Sambiloto extracts. Drinking water consumption (Sig.941), feed consumption (Sig.890), egg production (Sig.480) and feed conversion (sig.558) showed no difference. Based on the results of the study, the treatment of vaccines and extracts of meniran and Sambiloto gave a better immune response than without being vaccinated. Administration of meniran and Sambiloto extracts was able to maintain the level of immunity compared to no control.

Serological Evaluation of Antibody Titers After Vaccination Against COVID-19 in 18-44-Year-Old Individuals at a Tertiary Care Center.

Background The evaluation of the effectiveness of the vaccines (ChAdOx1-nCOV; Covishield and BBV-152; Covaxin) against coronavirus disease 2019 (COVID-19) is necessary to assess their efficacy. Because most antibodies that neutralize the coronavirus are directed against the receptor binding domain within the spike protein of the virus, these antibodies serve as markers for viral neutralizers and, in turn, for vaccine response. The present study aimed to evaluate the anti-neutralizing antibody(receptor binding domain (RBD)) and immunoglobulin G2 (IgG2) titers following the completion of the vaccination schedule (both vaccines) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methodology In this longitudinal prospective study, conducted in a tertiary care center, 30 sequentially (two doses) vaccinated study participants between the ages of 18 and 44 years were sampled for estimation of anti-RBD antibody titer and IgG2. All statistical analysis was done using SPSS version 20 (IBM Corp., Armonk, NY, USA). P-values less than 0.05 were considered significant. Results There was a statistically significant increase in the neutralizing antibody titer after one month of the second dose (z = -4.597, p < 0.001), while a significant decrease was seen in the IgG2 levels (z = -3.075, p = 0.002). The results showed a significant neutralizing effect of the vaccines being used, with Covishield being more effective than Covaxin. The levels of neutralizing antibodies were independent of all demographic variables such as age, sex, and body mass index. Conclusions This study evaluating the efficacy of the two vaccines, namely, Covishield and Covaxin, is the first of its kind in the state of Chhattisgarh. The results of this study are similar to previous studies conducted in India and outside India, concluding that Covishield is a more effective vaccine.

Assessment of mRNA Vaccine Immunogenicity in Solid Organ Transplant Recipients.

Background and Objectives: Solid organ transplant (SOT) recipients have a higher risk of suffering from severe Coronavirus (COVID-19) compared to the general population. Studies have shown impaired immunogenicity of mRNA vaccines in this high-risk population; thus, SOT recipients have been prioritized globally for primary and booster doses. Materials and Methods: We analyzed 144 SOT recipients who had previously received two doses of BNT162b2 or mRNA1273 vaccine, and who were subsequently vaccinated with a booster dose of the mRNA1273 vaccine. Humoral and cellular immune responses were measured 1 and 3 months after the second dose, and 1 month after the third dose. Results: One month after the second dose, 33.6% (45/134) of patients displayed a positive antibody response with a median (25th, 75th) antibody titer of 9 (7, 161) AU/mL. Three months after the second dose, 41.8% (56/134) tested positive with a median (25th, 75th) antibody titer of 18 (7, 251) AU/mL. After the booster dose, the seropositivity rate increased to 69.4% (93/134), with a median (25th, 75th) titer of 966 (10, 8027) AU/mL. The specific SARS-CoV-2 T-cell response was assessed in 44 randomly selected recipients 3 months after the second dose, and 11.4% (5/44) of them had a positive response. Following the third dose, 42% (21/50) tested positive. Side effects after the third dose were mild, with pain at the injection site being the most frequent adverse effect, reported by 73.4% of the recipients. Conclusion: Our study shows a mild delayed increase in antibody titer, three months after primary vaccination compared to one month after. It also shows a robust augmentation of humoral and specific T-cell responses after the booster dose, as well as the safety and tolerability of the mRNA vaccines in SOT recipients.

Under-diagnosis of vector-borne diseases among individuals suspected of having Scrub Typhus in South Korea.

Due to environmental and ecological changes and suitable habitats, the occurrence of vector-borne diseases is increasing. We investigated the seroprevalence of four major vector-borne pathogens in human patients with febrile illness who were clinically suspected of having Scrub Typhus (ST) caused by Orientia tsutsugamushi. A total of 187 samples (182 patient whole blood and sera samples, including 5 follow-up) were collected. Antibodies to Anaplasma phagocytophilum, Ehrlichia chaffeensis, Borrelia burgdorferi, and Bartonella henselae were tested by using indirect immunofluorescence assays. Molecular diagnoses were performed using real-time PCR. Of the 182 cases, 37 (20.3%) cases were designated as confirmed cases of ST, and the remaining 145 (79.7%) cases as other febrile diseases (OFDs). The seroprevalence of A. phagocytophilum, E. chaffeensis, B. burgdorferi, and B. henselae was 51.4% (19/37), 10.8% (4/37), 86.5% (32/37), and 10.8% (4/37) among the ST group, and 42.8% (62/145), 10.4% (19/145), 57.7% (105/145), and 15.9% (29/145) among the OFD group, respectively. There were no significant differences in the seroprevalence between the ST and the OFD groups. Considering the co-occurrence, 89.0% (162/182) had at least one antibody to tick-borne pathogens, 37.0% (60/162) were positive for two pathogens, 17.3% (28/162) for three pathogens, and 6.2% (10/162) for four pathogens. In real-time PCR, O. tsutsugamushi was positive in 16 cases [15 (40.5%) in ST group and 1 (2.2%) in OFD group], and the four other pathogens were negative in all cases except one confirmed as anaplasmosis. In evaluating the five follow-up samples, the appearance of new antibodies or an increase in the pre-existing antibody titers was detected. Our data highlighted that acute febrile illness and manifestations suggestive of a vector-borne infection must be recognized and further considered for coinfections in clinical practice and the laboratory.

Assessment of the humoral immune response in children after immunization with different types of inactivated influenza vaccines in the 2019-2020 season

Causing millions of cases worldwide every year, influenza is one of the most common respiratory infections. The effectiveness of influenza vaccination and the nature of the resulting immune response may vary depending on the vaccine composition and age group. Since children are at the highest risk of disease and act as the main carriers of influenza, the assessment of the immunological efficacy of vaccines in this group is crucial for controlling the epidemic. Therefore, this study aimed to evaluate the characteristics of the humoral immune response in children after immunization with various types of inactivated influenza vaccines. An observational study was conducted in the 2019-2020 season and involved 230 children (&lt; 18 years old) and a comparison group of 87 adults aged 18 to 60 years. The subjects, who provided informed consent to participate, were vaccinated with one of three vaccines (Grippol Plus, Sovigripp, or Ultrix) in an open-label fashion. The humoral immune response was assessed by measuring the hemagglutination inhibition (HI) titer in the paired sera taken before and three weeks after vaccination. The immunogenicity of the vaccines in the age group under 18, met the CPMP criteria for the assessment of inactivated influenza vaccines in terms of the fold increase in antibody titers and the proportion of individuals with seroconversion to all three components (A/H1N1pdm09, A/H3N2, and B/Victoria). Although 6 to 18-year-old participants showed a more robust immune response to the B/Victoria component compared to the adult participants (aged 18 to 60), it was insufficient to ensure that 70% of the participants have a protective antibody titer. A comparative analysis of the vaccines’ immunogenicity was carried out for a subgroup of children aged 6-18 who had initially low antibody levels at the time of vaccination. The analysis showed that the split vaccine Ultrix outperformed the adjuvanted vaccine Grippol Plus in generating an antibody response to the component B/Victoria; however, the antibody responses to the A/H1N1pdm09 and A/H3N2 components did not differ between the two vaccines. The children under 6 years of age demonstrated a less pronounced humoral immune response to vaccination compared with the other age groups, which may be due to the age-related characteristics of the immune system in children of preschool age.

Safety and efficacy of SNS-301 plus pembrolizumab in patients with advanced squamous cell carcinoma of the head and neck (SCCHN).

e18009 Background: Cancer vaccines may expand intratumoral CD8+ T cells, potentially increasing response rates to PD-1 blockade. SNS-301 is a bacteriophage-based cancer vaccine against aspartate β- hydroxylase (ASPH), a prevalent tumor-associated antigen. The objectives of this Phase 1/2 study were to evaluate the safety, immunogenicity and preliminary efficacy of SNS-301 plus pembrolizumab in patients (pts) not achieving tumor reductions on PD-1 blockade alone (Cohort A) or PD-1 blockade naïve patients (Cohort B). Methods: This trial enrolled SCCHN pts with locally advanced, unresectable or metastatic/recurrent ASPH+ tumors per screening immunohistochemistry. Intradermal SNS-301 (1x1011 particles) + pembrolizumab (200mg IV q3w or 400mg IV q6w) was administered to pts with stable disease (SD) or unconfirmed progressive disease on ongoing PD-1 blockade of at least 12 weeks duration in Cohort A, and anti-PD1/PD-L1 naïve patients in Cohort B. Each cohort utilized a Simon Two Stage design with ORR assessed per RECIST1.1 at 12 weeks as the primary endpoint. The null hypothesis (H0) was 5% ORR for Cohort A and 13.3% for cohort B. Enrollment of stage 2 was triggered if the ORR rate was ≥ 1 out of 15 initial evaluable patients (Cohort A) or ≥2 out of 15 (Cohort B). An initial “safety run-in” was instituted to ensure safety of the combination. Blood samples were collected to evaluate B and T cell responses using ELISA and ELISPOT assays, respectively. Results: Safety. No dose-limiting toxicities were identified in the “safety run-in” (initial 3 pts dosed). Overall, 25 pts were evaluable for safety assessment. 18 pts reported at least one treatment-emergent adverse event (TEAE), the majority of which were ≤ Grade 3. Grade 3 TRAEs included pruritus, rash, dehydration and QT prolongation. Three pts discontinued the study treatment due to TEAE and none were related to study treatment. There were three deaths reported during the follow-up period of the study and none were treatment related. Efficacy. 18 pts in Cohort A and 1 pt in Cohort B were evaluable for response per RECIST1.1 at 12 weeks. In Cohort A, one patient in Stage 1 had a PR, which triggered enrollment into Stage 2. In addition, 8 patients experienced SD as the best overall response. In Cohort B, a single PD-1/PD-L1 naïve patient was evaluable for efficacy and experienced a PR on the combination. Only a single pt in Cohort A experienced an AE of special interest (Grade 1 injection site pain). Pts treated with SNS-301 + pembrolizumab did not demonstrate significant ASPH-specific T-cell responses or increases in serum ASPH antibody titers. Conclusions: The combination of SNS-301 and pembrolizumab was well-tolerated with few treatment-related TEAEs. Importantly, pts treated with SNS-301 + pembrolizumab did not demonstrate ASPH-specific antibody or T-cell responses. Based on insufficient immunologic and clinical activity, the trial was terminated early. Clinical trial information: NCT04034225 .

Group 1 and group 2 hemagglutinin stalk antibody response according to age.

Antibodies elicited by seasonal influenza vaccines mainly target the head of hemagglutinin (HA). However, antibodies against the stalk domain are cross-reactive and have been proven to play a role in reducing influenza disease severity. We investigated the induction of HA stalk-specific antibodies after seasonal influenza vaccination, considering the age of the cohorts. A total of 166 individuals were recruited during the 2018 influenza vaccine campaign (IVC) and divided into groups: <50 (n = 14), 50-64 (n = 34), 65-79 (n = 61), and ≥80 (n = 57) years old. Stalk-specific antibodies were quantified by ELISA at day 0 and day 28 using recombinant viruses (cH6/1 and cH14/3) containing an HA head domain (H6 or H14) from wild bird origin with a stalk domain from human H1 or H3, respectively. The geometric mean titer (GMT) and the fold rise (GMFR) were calculated, and differences were assessed using ANOVA adjusted by the false discovery rate (FDR) and the Wilcoxon tests (p <0.05). All age groups elicited some level of increase in anti-stalk antibodies after receiving the influenza vaccine, except for the ≥80-year-old cohort. Additionally, <65-year-old vaccinees had higher group 1 antibody titers versus group 2 before and after vaccination. Similarly, vaccinees within the <50-year-old group showed a higher increase in anti-stalk antibody titers when compared to older individuals (≥80 years old), especially for group 1 anti-stalk antibodies. Seasonal influenza vaccines can the induction of cross-reactive anti-stalk antibodies against group 1 and group 2 HAs. However, low responses were observed in older groups, highlighting the impact of immunosenescence in adequate humoral immune responses.

Antibody Response in The Blood of Cantang Grouper Infected by Viral Nervous Necrosis with Recombinant Protein Chlorella Vulgaris Vaccination

Cantang grouper (Epinephelus sp.) is one of the Export Oriented commodities which is a mainstay in increasing Indonesian mariculture production. The disease that causes many deaths in cantang grouper is Viral Nervous Necrosis. One of the most effective ways is by giving vaccines to fish. This study aims to develop a recombinant protein Chlorella vulgaris vaccine with the addition of an adjuvant to increase the immunity of cantang grouper infected with VNN. The method used was experimental with a Completely Randomized Design (CRD) consiting of seven treatments and three replications, namely (K+) cantang grouper infected with VNN, (T1) Healthy cantang grouper was given 33 µl of vaccine, (T2) Healthy cantang grouper was given vaccine of 66 µl, (T3) Healthy cantang grouper was given 112 µl of vaccine, (T4) Healthy cantang grouper was given 33 ul of vaccine and then tested against Viral Nervous Necrosis, (T5) Healthy cantang grouper was given 66 ul vaccine and then tested against Viral Nervous Necrosis, (T6) Healthy cantang grouper was given 112 ul vaccine and then tested against Viral Nervous Necrosis. The fish used were 8-10 cm in size and were reared for 56 days. The results showed that the Chlorella vulgaris protein recombinant vaccine with the addition of adjuvant gave a very significant effect on the immunity of cantang grouper infected with VNN with the best dose of 33 µl (T4) seen from the relative protection level (RPS) (75,6%), survival of cantang grouper (78%) after challenge test and a significant increase in antibody titer.

Immunogenicity of quadrivalent meningococcal conjugate vaccine in frequent platelet donors

AbstractFrequent plateletpheresis is associated with severe lymphopenia of uncertain clinical significance. We assessed the functional impact of frequent platelet donations and associated lymphopenia on the response to neoantigens. We conducted a prospective study of 102 platelet donors (HIV uninfected) who were naive to meningococcal vaccination recruited at Brigham and Women’s Hospital. One dose of quadrivalent meningococcal conjugate vaccine was administered. Seroresponse was defined as a fourfold increase of serum bactericidal antibody titers and seroprotection was defined as postvaccination titers of ≥1:8, for each of the 4 vaccine antigens (A, C, W, and Y). Mean age of participants was 61 years, 69% were male, and medial number of platelet donations in prior year was 14 (interquartile range, 4-20). Frequent platelet donors had a low CD4 count (14% with ≤200/μL and 34% with ≤350/μL). Seroresponse rates varied from 68% for serogroup Y to 86% for serogroup A and were higher for participants with baseline titers of <1:8. Postvaccination seroprotection rates varied from 76% for serogroup Y to 96% for serogroup A. After adjustments for age, sex, and frequent donations, lower total lymphocyte or lower CD4 counts were not associated with lower responses. These data suggest no impairment by plateletpheresis-associated lymphopenia on response to these neoantigens. This trial was registered at www.clinicaltrials.gov as #NCT04224311.

Understanding the effect of temperature downshift on CHO cell growth, antibody titer and product quality by intracellular metabolite profiling and in vivo monitoring of redox state.

The strategy of temperature downshift has been widely used in the biopharmaceutical industry to improve antibody production and cell-specific production rate (qp ) with Chinese hamster ovary cells (CHO). However, the mechanism of temperature-induced metabolic rearrangement, especially important intracellular metabolic events, remains poorly understood. In this work, in order to explore the mechanisms of temperature-induced cell metabolism, we systematically assessed the differences in cell growth, antibody expression, and antibody quality between high-producing (HP) and low-producing (LP) CHO cell lines under both constant temperature (37°C) and temperature downshift (37°C→33°C) settings during fed-batch culture. Although the results showed that low-temperature culture during the late phase of exponential cell growth significantly reduced the maximum viable cell density (p < 0.05) and induced cell cycle arrest in the G0/G1 phase, this temperature downshift led to a higher cellular viability and increased antibody titer by 48% and 28% in HP and LP CHO cell cultures, respectively (p < 0.001), and favored antibody quality reflected in reduced charge heterogeneity and molecular size heterogeneity. Combined extra- and intra-cellular metabolomics analyses revealed that temperature downshift significantly downregulated intracellular glycolytic and lipid metabolic pathways while upregulated tricarboxylic acid (TCA)cycle, and particularly featured upregulated glutathione metabolic pathways. Interestingly, all these metabolic pathways were closely associated with the maintenance of intracellular redox state and oxidative stress-alleviating strategies. To experimentally address this, we developed two high-performance fluorescent biosensors, denoted SoNar and iNap1, for real-time monitoring of intracellular nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide + hydrogen (NAD+ /NADH) ratio and nicotinamide adenine dinucleotide phosphate (NADPH) amount, respectively. Consistent with such metabolic rearrangements, the results showed that temperature downshift decreased the intracellular NAD+ /NADH ratio, which might be ascribed to the re-consumption of lactate, and increased the intracellular NADPH amount (p < 0.01) to scavenge intracellular reactive oxygen species (ROS) induced by the increased metabolic requirements for high-level expression of antibody. Collectively, this study provides a metabolic map of cellular metabolic rearrangement induced by temperature downshift and demonstrates the feasibility of real-time fluorescent biosensors for biological processes, thus potentially providing a new strategy for dynamic optimization of antibody production processes.

Microanatomical lipid niche controls intestinal memory B cell migration and effector function

Abstract Enteric infections are a leading global burden, yet few oral vaccines elicit long-lasting immunity and prevent disease, likely due to our lack of understanding of intestinal immunological memory. Long-lived memory B cells can be rapidly reactivated to differentiate into plasma cells, thus further increasing antibody titers and mediating host protection. Such long-term protection requires memory B cells to migrate and persist in sub-anatomical niches within secondary lymphoid organs. While survival niches have been described for memory B cells in lymph nodes and spleen, no niche have been identified in mucosal lymphoid organs, such as Peyer’s patches (PPs). Here, we show that memory B cells require positioning in the PP subepithelial dome (SED) for maintenance and effector function. In PPs, memory B cells express the migratory receptors EBI2, which binds the oxysterol 7alpha, 25-hydroxycholesterol, and CCR6, which recognizes the chemokine CCL20. Both ligands are present in PPs and drive memory B cell migration in vitro. Conditional removal of EBI2 from memory B cells, either in a constitutive or acute fashion, alters their zonation in PPs, reduces their persistency, and impairs their antigen-specific response. While most memory B cells in PPs are IgA+, IgA B cell receptor expression is dispensable for memory B cell positioning in the SED. Using conditional mice for the enzymes generating the oxysterol gradient and cell specific Cre lines, we are currently mapping the cellular and metabolic requirements for EBI2 dependent memory B cell maintenance and effector function in PPs. Understanding the mechanisms for memory B cell persistence is fundamental to our understanding of the intestinal B cell memory response against pathogens. Previously supported by training grants from NIH (5 T32 AI 132152-2, 5 T32 AI 007349-29)

Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection.

Abstract Virus-specific neutralizing antibodies are generally accepted as a correlate of protection against infection, though many questions remain about which components of the immune response protect against SARS-CoV-2 infection. We longitudinally measured Spike receptor binding domain (RBD)-specific serum IgG and nucleocapsid protein (NP)-specific serum IgG in a human cohort immunized with the Pfizer BNT162b2 vaccine. Serum samples were collected and stored at −80 °C. Antibody titers were quantitated using an endpoint dilution ELISA and reported as inverse titers. A four-fold or greater increase in NP-specific antibody titers was used as serological marker of clinical infection at some point prior to the sample collection. Using the RBD-specific IgG titer measured in participants’ serum collected prior to seroconversion for NP, we were able to calculate a protective threshold titer for RBD-specific IgG. We calculated the rate of decay of antibodies in participants who did not exhibit a four-fold increase in NP-specific IgG, i.e. had no serological evidence of infection, and found that, on average, the RBD-specific IgG response waned below the protective threshold by four months following vaccination. These data highlight the need for a more durable immune response to vaccination which may require different adjuvants, dosages, or vaccination schedules. This work was supported by The Robert M. Hearin Foundation, The Bower Foundation, and James L. Barksdale.

Heterologous versus homologous boosting regimens elicit qualitatively distinct, BA.5 cross reactive T cells in transplant recipients

Abstract The Omicron BA.5 subvariant of SARS-CoV-2 markedly escapes neutralizing antibodies induced by vaccination due to mutations in the Spike (S) protein. Solid organ transplant recipients (SOTRs) suffer high COVID-19 morbidity, yet show poor ancestral strain recognition after COVID-19 vaccination. CD8+ T cell responses may provide a crucial second line of defense. Therefore, it is critical to understand which vaccine regimens induce robust, conserved T cell responses. We evaluated anti-S IgG titers, subvariant pseudo-neutralization, and S-specific CD4 and CD8 T cell responses in SOTRs following homologous mRNA (mRNA-1273 or BNT16b2) or heterologous Ad26.COV2.S (JNJ-78436735) boosting. Homologous boosting with three mRNA doses induced the highest anti-S IgG titers. However, antibodies induced by both vaccine regimens demonstrated significantly lower pseudo-neutralization against BA.5 compared to the ancestral strain. In contrast, S-specific T cells maintained cross-reactivity against BA.5 compared to ancestral recognition. Homologous boosting induced higher polyfunctional CD4 T cells with phenotypes associated with metabolic and immunologic activation. Comparing two mRNA platforms, mRNA-1273 induced significantly higher IL-21+ peripheral T follicular helper cells and increased antibody titers compared to BNT16b2. Heterologous boosting with Ad26.COV2.S did not increase CD8 responses compared to homologous boosting, as CD8 responses were low across all individuals. These data demonstrate that boosting with the ancestral strain can induce cross-reactive T cell responses against emerging variants of concern in SOTRs, but currently available boosting strategies do not induce robust CD8 T cell responses. U01AI138897 U54CA260491

Immunogenicity and safety of mixed COVID-19 vaccine regimens in patients with immune-mediated inflammatory diseases: a single-centre prospective cohort study

ObjectiveAmong persons with immune-mediated inflammatory diseases (IMIDs) who received SARS-CoV-2 vaccines, we compared postvaccine antibody responses and IMID disease activity/states.DesignSingle-centre prospective cohort study.SettingSpecialty ambulatory clinics in central Canada.ParticipantsPeople with inflammatory...

Recurrent GRAF1 Antibody Encephalitis in Woman with History of Cancer and Powassan Encephalitis (P4-5.012)

<h3>Objective:</h3> To review details of a rare presentation of autoimmune encephalitis with antibody to GRAF1, which is rare and with little information about its origin or associated clinical syndrome, and educate clinicians to identify similar presentations early to allow effective treatment and prognostic counseling for patients and their family. <h3>Background:</h3> This case details presentation of a rare cause of autoimmune encephalitis with antibodies to GTPase regulator associated with focal adhesion kinase-1 (GRAF1). Reports in the literature may group this with other anti-Ca channel antibodies, and often associate it with an ataxic clinical syndrome. Little is known about the origin of these antibodies, as it is not always associated with malignancy or specific systemic conditions. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 68 year old woman with a history of breast and cervical cancer, as well as Powassan encephalitis had recurrent episodes of encephalitis with prominent confusion, and was found to have a high titer of antibody to GRAF1 in her CSF with each clinical episode. She unfortunately did not respond well to immunosuppressive medications or IVIG, and passed away on hospice. The details of this case report highlight the clinical features associated with this case of GRAF1 antibody encephalitis and poses questions about whether cancer or prior CNS infection may be the origin of these antibodies, as our patient had a history or Powassan encephalitis. It is also not clear whether serial CSF testing can be used as maintenance to guide management. <h3>Conclusions:</h3> GRAF1 antibody encephalitis is a poorly understood cause of autoimmune encephalitis, without a consistent associated clinical syndrome, or associated condition that may be a source of the increased antibody titer. We pose the question whether this can be a post-infectious entity, and highlight a case of encephalitis which had recurrent episodes before becoming progressive and refractory to treatment. <b>Disclosure:</b> Dr. Dobson has nothing to disclose. Dr. Crissinger has nothing to disclose.

Efficacy, effectiveness and safety of the adjuvanted influenza vaccine in the population aged 65 or over

Most of the complications and deaths related to seasonal flu occur in the elderly population (≥65 years) with comorbidities, and the influenza vaccine is the most effective way to prevent them. Immunization is less effective in older adults due to immunosenescence. MF59-adjuvanted vaccines, designed to improve the magnitude, persistence and amplitude of the immune response in elderly people, have been used in clinical practice since 1997 in their trivalent formulation and, since 2020, in their tetravalent formulation. Data from various studies show that these vaccines are not only safe for all age groups, with a reactogenicity profile similar to that of the conventional vaccine, but also that they are especially effective in boosting the immune response in the population aged 65 or over by increasing antibody titers after vaccination and significantly reducing the risk of hospital admission. Adjuvanted vaccines have been shown to provide cross-protection against heterologous strains and to be as effective as the high-dose vaccine in the population aged 65 or over. In this review, the scientific evidence on the efficacy and effectiveness of the MF59-adjuvanted vaccine in real clinical practice in people ≥65 years of age is analyzed through a narrative and descriptive review of the literature with data from clinical trials, observational studies and systematic reviews or meta-analysis.