Ab Titers Research Articles

A case-control study to assess the association of Alopecia areata with thyroid dysfunction and thyroid Autoimmunity.

Several previous studies have suggested a positive association between Alopecia Areata and thyroid disorders. However, there is a paucity of such studies in our country. Our study aimed to know the frequency of thyroid dysfunction and thyroid autoimmunity in patients reporting to Dermatology Outdoors with Alopecia Areata (AA) and to compare it with normal controls. This was a Case-Control study conducted at the Dermatology outpatient of a tertiary care hospital in Pakistan. 102 patients with AA and 102 age and sex-matched controls were enrolled. The age of onset of the disease, the involved sites and the presence of other associated diseases were noted. Venous blood samples were taken from patients and controls for Thyroid function tests and Anti- Thyroid peroxidase antibodies (Anti-TPO Ab). The data was analyzed using Statistical Package for Social Sciences (SPSS) version 23. The mean age of onset of the disease was 30.37±12.53. 91.2% of patients had the classic patch type of AA. The most commonly involved site was Scalp. Associated diseases were found in eight (7.8%) patients. Thyroid dysfunction was found in two patients and none of the Controls. Both the patients had Subclinical thyroid disease. The p-value was 0.157, which was not statistically significant. Thyroid autoimmunity (raised Anti-TPO Ab titre) was detected in five (4.90%) patients and none of the Controls. The p-value was 0.024, which was statistically significant. AA is significantly associated with Thyroid autoimmunity but there is no significant association between AA and clinical or subclinical thyroid disease.

Association of High TPO Antibody Titer with Differentiated Thyroid Carcinoma: A Case-Control Study

Background: The most common well-differentiated thyroid carcinomas are papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). PTC accounts for 80–90% of all thyroid cancers, and follicular carcinoma accounts for 10–15% of all thyroid cancers. Common established risk factors for thyroid carcinoma are head-neck irradiation, a positive family history, and a few genetic disorders. High anti-thyroglobulin antibodies (TgAb) have already been established as predictive markers for thyroid carcinoma, but anti-thyroid peroxidase antibodies (TPO Ab) have not been established as predictive markers till now. Objective: To find out the association of high TPO Ab titer with differentiated thyroid carcinoma (DTC). Patients and Methods: This case-control study was carried out at the National Institute of Nuclear Medicine & Allied Sciences (NINMAS), Dhaka, from September 2020 to November 2021. A total of 52 cytologically diagnosed DTC patients who underwent thyroidectomy were selected as cases. Another 52 age- and sex-matched healthy individuals who had sonographically normal thyroid glands and a biochemically euthyroid state were selected as controls. The total number of participants was 104. Written informed consent was obtained from each of the participants. A detailed history was taken, and a thorough clinical examination was carried out on each patient. High resolution ultrasonography (HRUS) of the thyroid gland, serum thyroid-stimulating hormone (TSH) level, and fine needle aspiration cytology (FNAC) report of the thyroid nodule of each participant were collected. Serum TPO antibody levels were measured in patients with DTC prior to thyroid surgery, as well as in the control group, in the NINMAS laboratory using the CLIA method. After the collection of all the required data, analysis was done by SPSS 24.0. Results: The mean age of the cases was 35.8 ± 13.3 years and 34.6 ± 13.0 years in the control groups. Female patients were predominant in both the case and control groups (63.5% and 69.2%, respectively). Both groups were statistically almost similar in terms of age and sex. Around 46.2 % (n=24) patients in the case group had high serum TPO Ab levels and 15.4 % (n=8) of participants in the control group had high serum TPO Ab levels. The mean serum TPO Ab level in the case group was 306.77± 452.57 U/mL, and the mean serum TPO Ab level in the control group was 75.85±181.47 U/mL. Serum TPO antibody level was significantly higher in the case group compared to the control group (306.77±452.57 vs 75.85±181.47 U/mL, p = 0.001). Conclusion: There was a significant association of high TPO Ab titer found with DTC Bangladesh J. Nuclear Med. 26(1): 34-38, 2023

Antibody titer levels and the effect on subsequent SARS-CoV-2 infection in a large US-based cohort

Despite a growing amount of data around the kinetics and durability of the antibody response induced by vaccination and previous infection, there is little understanding of whether or not a given quantitative level of antibodies correlates to protection against SARS-CoV-2 infection or reinfection. In this study, we examine SARS-CoV-2 anti-spike receptor binding domain (RBD) antibody titers and subsequent SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) tests in a large cohort of US-based patients. We analyzed antibody test results in a cohort of 22,204 individuals, 6.8% (n = 1,509) of whom eventually tested positive for SARS-CoV-2 RNA, suggesting infection or reinfection. Kaplan-Meier curves were plotted to understand the effect of various levels of anti-spike RBD antibody titers (classified into discrete ranges) on subsequent RT-PCR positivity rates. Statistical analyses included fitting a Cox proportional hazards model to estimate the age-, sex- and exposure-adjusted hazard ratios for S antibody titer, using zip-code positivity rates by week as a proxy for COVID-19 exposure. It was found that the best models of the temporally associated infection risk were those based on log antibody titer level (HR = 0.836 (p < 0.05)). When titers were binned, the hazard ratio associated with antibody titer >250 Binding Antibody Units (BAU) was 0.27 (p < 0.05, 95% CI [0.18, 0.41]), while the hazard ratio associated with previous infection was 0.20 (p < 0.05, 95% CI [0.10, 0.39]). Fisher exact odds ratio (OR) for Ab titers <250 BAU showed OR = 2.84 (p < 0.05; 95% CI: [2.30, 3.53]) for predicting the outcome of a subsequent PCR test. Antibody titer levels correlate with protection against subsequent SARS-CoV-2 infection or reinfection when examining a cohort of real-world patients who had the spike RBD antibody assay performed.

Mosaic RBD nanoparticles induce intergenus cross-reactive antibodies and protect against SARS-CoV-2 challenge.

Recurrent spillovers of α- and β-coronaviruses (CoV) such as severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome-CoV, SARS-CoV-2, and possibly human CoV have caused serious morbidity and mortality worldwide. In this study, six receptor-binding domains (RBDs) derived from α- and β-CoV that are considered to have originated from animals and cross-infected humans were linked to a heterotrimeric scaffold, proliferating cell nuclear antigen (PCNA) subunits, PCNA1, PCNA2, and PCNA3. They assemble to create a stable mosaic multivalent nanoparticle, 6RBD-np, displaying a ring-shaped disk with six protruding antigens, like jewels in a crown. Prime-boost immunizations with 6RBD-np in mice induced significantly high Ab titers against RBD antigens derived from α- and β-CoV and increased interferon (IFN-γ) production, with full protection against the SARS-CoV-2 wild type and Delta challenges. The mosaic 6RBD-np has the potential to induce intergenus cross-reactivity and to be developed as a pan-CoV vaccine against future CoV spillovers.

Intermediate Levels of Pre-Existing Protective Antibody Allow Priming of Protective T Cell Immunity against Influenza.

Overcoming interfering impacts of pre-existing immunity to generate universally protective influenza A virus (IAV)-specific T cell immunity through vaccination is a high priority. In this study, we passively transfer varied amounts of H1N1-IAV-specific immune serum before H1N1-IAV infection to determine how different levels of pre-existing Ab influence the generation and protective potential of heterosubtypic T cell responses in a murine model. Surprisingly, IAV nucleoprotein-specific CD4 and CD8 T cell responses are readily detected in infected recipients of IAV-specific immune serum regardless of the amount transferred. When compared with responses in control groups and recipients of low and intermediate levels of convalescent serum, nucleoprotein-specific T cell responses in recipients of high levels of IAV-specific serum, which prevent overt weight loss and reduce peak viral titers in the lungs, are, however, markedly reduced. Although detectable at priming, this response recalls poorly and is unable to mediate protection against a lethal heterotypic (H3N2) virus challenge at later memory time points. A similar failure to generate protective heterosubtypic T cell immunity during IAV priming is seen in offspring of IAV-primed mothers that naturally receive high titers of IAV-specific Ab through maternal transfer. Our findings support that priming of protective heterosubtypic T cell responses can occur in the presence of intermediate levels of pre-existing Ab. These results have high relevance to vaccine approaches aiming to incorporate and evaluate cellular and humoral immunity towards IAV and other viral pathogens against which T cells can protect against variants escaping Ab-mediated protection.

Ophthalmologic clinical features of ocular myasthenia gravis.

To investigate the clinical features of ocular myasthenia gravis (OMG) in ophthalmology. A total of 28 patients with ptosis or diplopia who were followed for at least 6 months between March 2016 and February 2022 were included in this study. The clinical symptoms of the patients and test results were analyzed. According to the positivity of serologic or electrophysiologic test, these patients were divided into 2 groups (positive and negative OMG results) and according to the clinical symptoms of diplopia or ptosis for comparison. Ptosis, diplopia, and both ptosis and diplopia were present in 6 (21.43%), 14 (50.0%), and 8 (28.57%) patients, respectively. Acetylcholine receptor auto-antibody (AchR Ab) was positive in 16 (57.14%) of 28 patients and the ice test was positive in 13 (92.86%) of 14 patients with ptosis. Abnormal thymic lesions were presented in 7 (25.0%) patients, and a definite improvement in response to pyridostigmine was observed in 27 (100.0%) patients. Both ptosis and diplopia were significantly higher in the group with positive results than that in the negative results group (P = .025). In addition, both horizontal and vertical diplopia was significantly higher in the group with AchR Ab titer > 5.0 than that in the group with AchR Ab titer < 5.0 (P = .041). After excluding cranial nerve palsy, if there is ptosis and diplopia, especially vertical diplopia, the possibility of OMG should be considered.

TNF-α Limits Serological Memory by Disrupting the Bone Marrow Niche.

Both infection and autoimmune disease can disrupt pre-existing Ab titers leading to diminished serological memory, yet the underlying mechanisms are not well understood. In this article, we report that TNF-α, an inflammatory cytokine, is a master regulator of the plasma cell (PC) niche in the bone marrow (BM). Acute rTNF-α treatment depletes previously existing Ab titers after vaccination by limiting PC occupancy or retention in the BM. Consistent with this phenomenon, mice lacking TNF-α signaling have elevated PC capacity in the BM and higher Ab titers. Using BM chimeric mice, we found that PC egress from the BM is regulated in a cell-extrinsic manner, by radiation-resistant cells via TNF-α receptor 1 signaling, leading to increased vascular permeability and CD138 downregulation on PCs. PC motility and egress in the BM are triggered within 6 h of recombinant TNF-α treatment. In addition to promoting egress, TNF-α signaling also prevented re-engraftment into the BM, leading to reduced PC survival. Although other inflammatory stimuli can promote PC egress, TNF-α signaling is necessary for limiting the PC capacity in the BM. Collectively, these data characterize how TNF-α-mediated inflammation attenuates the durability of serological memory and shapes the overall size and composition of the Ab-secreting cell pool in the BM.

Efficacy of different live infectious bursal disease vaccines on antibodies to infectious bursal disease virus and Newcastle disease vaccine La Sota in ISA brown chicks

Aim: In this study, the efficacy of five commercial live infectious bursal disease (IBD) vaccines on antibody (Ab) decay and response to a very virulent IBD virus (vvIBDV) and Newcastle disease (ND) vaccine La Sota in ISA Brown chicks were assessed. Methods: Seven groups of chickens (A, B, C, D, E, F, and G) comprising 50 chicks each were used for the study. Groups A, B, C, D, and E were vaccinated with Bur-706, MB-Strain, B87-Strain, Bursa-B2K, and HIPRA live IBD vaccines, respectively, at 14 and 28 days of age (doa), and challenged with a vvIBDV at 35 doa. Groups F and G served as positive and negative controls, respectively. At 42 doa, all groups were vaccinated with ND vaccine La Sota. Blood was collected at 1, 7, 14, 21, 28, 35, 42, and 49 doa, and serum was harvested. The serum was analyzed for IBD virus (IBDV) Ab titres using enzyme-linked immunosorbent assay (ELISA) and ND Ab titres using a haemagglutination inhibition (HI) test. Results: Results revealed significantly (p &lt; 0.05) higher ELISA IBDV Ab titres in groups A to E than in F from 21 to 49 doa, with the highest in group D. At 49 doa, there was significantly (p &lt; 0.05) higher HI Ab titre in groups A to E than in F with the highest in group D. In conclusion, the live IBDV vaccines were immunogenic following vaccination. The vaccines decreased the decay of IBDV Ab and mitigated the decreased response to ND vaccine La Sota in the chicks following the vvIBDV challenge, with more effects induced by Bursa-B2K. Conclusion: The live vaccines (Bur-706, MB-Strain, B87-Strain, Bursa-B2K, and HIPRA) were immunogenic following vaccination.

Immune responses to inactivated COVID-19 vaccine were decreased in Chinese patients with chronic respiratory diseases.

Purpose: The effectiveness of inactivated vaccines against acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the causative agent of coronavirus disease 2019 (COVID-19), has become a global concern. Hence, the aim of this study was to evaluate vaccine safety and to assess immune responses in individuals with chronic respiratory disease (CRD) following a two-dose vaccination. Methods: The study cohort included 191 participants (112 adult CRD patients and 79 healthy controls [HCs]) at least 21 (range, 21-159) days after a second vaccination. Frequencies of memory B cells (MBCs) subsets and titers of SARS-CoV-2 neutralizing antibodies (NAbs) and anti-receptor binding domain (RBD) IgG antibodies (Abs) were analyzed. Results: As compared to the HCs, CRD patients had lower seropositivity rates and titers of both anti-RBD IgG Abs and NAbs, in addition to lower frequencies of RBD-specific MBCs (all, p < 0.05). At 3 months, CRD patients had lower seropositivity rates and titers of anti-RBD IgG Abs than the HCs (p < 0.05). For CoronaVac, the seropositivity rates of both Abs were lower in patients with old pulmonary tuberculosis than HCs. For BBIBP-CorV, the seropositivity rates of CoV-2 NAbs were lower in patients with chronic obstructive pulmonary disease than HCs (all, p < 0.05). Meanwhile, there was no significant difference in overall adverse events between the CRD patients and HCs. Univariate and multivariate analyses identified the time interval following a second vaccination as a risk factor for the production of anti-RBD IgG Abs and CoV-2 NAbs, while the CoronaVac had a positive effect on the titers of both Abs. Female was identified as a protective factor for CoV-2 NAb levels. Conclusion: Inactivated COVID-19 vaccines were safe and well tolerated by CRD patients but resulted in lower Ab responses and the frequencies of RBD-specific MBCs. Therefore, CRD patients should be prioritized for booster vaccinations.

Relationship between CTLA4, TNF-α and PTPN22 gene polymorphism and the serum levels of antithyroglobulin and antiperoxidase antibodies in autoimmune thyroiditis

&lt;abstract&gt; &lt;p&gt;Autoimmune thyroiditis (AIT) is a chronic inflammatory that involves hyperactivation of the immune system against the thyroid gland, recognizing it as "nonself”. The aim of this research was to identify the relationships between genetic polymorphism in &lt;italic&gt;CTLA4&lt;/italic&gt;, &lt;italic&gt;TNF-α&lt;/italic&gt; and &lt;italic&gt;PTPN22&lt;/italic&gt; genes and the manifestation of AIT and levels of antithyroglobulin antibody (anti-TG Ab) and thyroid peroxidase antibody (anti-TPO Ab). The study was conducted during 2014–2020 and included 64 men and 106 women aged between 18 and 64 years with AIT. The control group consisted of 65 people (26 men, 39 women, aged between 20 and 65 years) without any thyroid pathologies or other autoimmune diseases. For molecular genetic analysis, real-time quantitative RT-PCR was used with fluorescently labeled FAM probes on a detection system CFX96 (BioRad). The results demonstrated that patients with the GG genotype and the G allele of the +49A/G polymorphism in the &lt;italic&gt;CTLA4&lt;/italic&gt; gene have significantly higher titers of anti-TG Ab. High titers of anti-TG Ab were detected in 22.4% of patients with the GG genotype (p = 0.005, χ2 = 7.86, OR = 0.237, 95% CI = 0.088–0.635), and in 55.6% of patients with the G allele (p = 0.0012, χ2 = 10.43, OR = 0.360, 95%, СI = 0.192–0.674). At the same time, the A allele of the +49A/G polymorphism is significantly more common in patients with normal anti-TG Ab values—in 68.1% of individuals (p = 0.0012, χ2 = 10.43, OR= 2.78, 95%, CI = 1.484–5.207). The results of the study indicate the prognostic significance of the G allele and the GG genotype of the +49A/G polymorphism of the &lt;italic&gt;CTLA4&lt;/italic&gt; gene predicting the probability of occurrence of anti-TG and anti-TPO antibodies.&lt;/p&gt; &lt;/abstract&gt;

Low Neutralizing Activities to the Omicron Subvariants BN.1 and XBB.1.5 of Sera From the Individuals Vaccinated With a BA.4/5-Containing Bivalent mRNA Vaccine.

The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has provided insights for updating current coronavirus disease 2019 (COVID-19) vaccines. We examined the neutralizing activity of Abs induced by a BA.4/5-containing bivalent mRNA vaccine against Omicron subvariants BN.1 and XBB.1.5. We recruited 40 individuals who had received a monovalent COVID-19 booster dose after a primary series of COVID-19 vaccinations and will be vaccinated with a BA.4/5-containing bivalent vaccine. Sera were collected before vaccination, one month after, and three months after a bivalent booster. Neutralizing Ab (nAb) titers were measured against ancestral SARS-CoV-2 and Omicron subvariants BA.5, BN.1, and XBB.1.5. BA.4/5-containing bivalent vaccination significantly boosted nAb levels against both ancestral SARS-CoV-2 and Omicron subvariants. Participants with a history of SARS-CoV-2 infection had higher nAb titers against all examined strains than the infection-naïve group. NAb titers against BN.1 and XBB.1.5 were lower than those against the ancestral SARS-CoV-2 and BA.5 strains. These results suggest that COVID-19 vaccinations specifically targeting emerging Omicron subvariants, such as XBB.1.5, may be required to ensure better protection against SARS-CoV-2 infection, especially in high-risk groups.

Identification of celiac disease associated IgA nephropathy by IgA anti-tissue transglutaminase2 antibody deposits in archived formalin-fixed tissues.

The causal association between IgA nephropathy (IgAN) and celiac disease (CeD) is based on their clinical coexistence. In this prospective study, we screened patients with IgAN for CeD and explored the utility of analysis of IgA anti-TG2 antibody deposits, for establishing a causal association. Biopsy-proven patients of IgAN were screened for serum IgA anti-tissue transglutaminase antibody (IgA anti-tTG Ab) titer and thereafter were invited to undergo endoscopic duodenal biopsy. Corresponding duodenal and kidney biopsies were subjected to IgA anti-TG2 antibody colocalization study using dual-color immunohistochemistry and immunofluorescence techniques. Additionally, kidney biopsies from 105 patients with IgAN who did not give consent for serology analysis, 30 non-IgA nephropathies, and 10 normal controls were also included. Dual-color-stained slides were interpreted based on stain distribution and intensity scores, and Pearson's index >0.3-1 on confocal imaging was considered significant. Of a cohort of 151 patients with IgAN, 32 consented to undergo sero-screening and 5 of them had high serum anti-tTG Ab titer. Two out of the latter consented to endoscopic duodenal biopsies, in whom modified Marsh grade 3b changes were identified. Strong IgA anti-TG2 antibody deposits were noted in the kidney and duodenal biopsies of these patients. One patient out of non-consenting 105 patients with IgAN and 3 out of 30 patients with other non-IgA nephropathies also showed IgA anti-TG2 deposits. None of the healthy kidney tissues showed IgA anti-TG2 Ab deposits. Co-localized IgA anti-TG2 deposits in the kidney biopsies in patients with IgAN help to establish a pathogenic link with CeD. A small proportion of patients with IgAN have associated CeD.

Bartonella henselae Infective Endocarditis: A Rare Cause of Pauci-Immune Necrotizing Glomerulonephritis—A Case Report

Bartonella sp. are the most common causes of culture-negative infective endocarditis (IE) cases in the United States. Although, infection-related glomerulonephritis can frequently mimic primary vasculitis due to pauci-immune pattern, majority of previously reported cases of Bartonella henselae-associated glomerulonephritis have immune-complex deposits on immunofluorescence. We present a rare case of B henselae IE-related pauci-immune necrotizing glomerulonephritis. Timely recognition of this atypical presentation led to appropriately directed medical therapy. A 33-year-old Caucasian male with a history of human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART), alcohol abuse, previous subarachnoid hemorrhage (SAH), and recent wisdom tooth extraction (on amoxicillin) was transferred from an outside hospital for further evaluation of severe headache. He was diagnosed with an SAH and right anterior cerebral artery mycotic aneurysm. The serum creatinine at the outside hospital was 292 umol/L (3.3 mg/dL) with a previously normal baseline around 2 years ago. The serum creatinine at our institution was 256 umol/L (3.0 mg/dL). The urinalysis demonstrated +100 protein, +3 blood and 29 red blood cells/high power field. The urine protein creatinine ratio (UPC) was 1.7 g/g. Serologic evaluation was positive for a low C4 10.2 mg/dL, elevated rheumatoid factor 40 IU/mL and an elevated proteinase 3 (PR-3) antineutrophilic cytoplasmic antibodies (ANCA Ab) 4.0 U/mL. A transesophageal echocardiogram (TEE) showed echo densities on both mitral and aortic valve. Blood cultures were negative. Further serologic evaluation was positive for B henselae IgG titer of 1:2560 (normal <1:320) with a negative IgM titer. A percutaneous kidney biopsy revealed pauci-immune necrotizing glomerulonephritis, with 14/16 glomeruli globally sclerotic, and 2 glomeruli with active segmental necrotizing lesions. There was no evidence of immune-complex deposition on immunofluorescence or electron microscopy. Clinical findings were consistent with B henselae IE associated mycotic aneurysm and necrotizing glomerulonephritis. Empiric treatment for an active glomerulonephritis with immunosuppressive agents was deferred on admission, given concern for an underlying infectious process and mycotic aneurysms in an HIV-positive patient. He received antibiotic treatment with doxycycline and ceftriaxone with gentamicin for synergy. Despite this, the mitral and aortic valve regurgitation worsened, and he developed congestive heart failure requiring aortic valve replacement and mitral valve repair. The explanted aortic valve was positive for B henselae by polymerase chain reaction (PCR) confirming the diagnosis of B henselae IE. Immunosuppression was deferred due to timely identification of an atypical presentation of B henselae-associated ANCA antibodies-positive, pauci-immune necrotizing glomerulonephritis. A course of antibiotic treatment resulted in improved renal functions along with undetectable B henselae and PR3 Ab titers. The serum creatinine decreased to 176 umol/L (2 mg/dL) and remained stable 12 months after discharge. B henselae IE should be suspected in patients with pauci-immune necrotizing glomerulonephritis and culture-negative IE. This is imperative for optimal decision making in the management of such patients. Having high clinical suspicion can avoid unnecessary and potentially deleterious use of immunosuppressive agents.

1951. Guiding COVID-19 Booster Vaccinations by COVID-19 Quantitative Spike Ig Antibody Titers Regardless of HIV Status, Immunosuppression, and Age

Abstract Background In-vitro neutralizing antibody (Ab) titers correlated with ∼250 IU/mL Spike Ig Ab level for the Delta COVID-19 variant, establishing the 2021 French and Swiss cutoff for booster guidance. In a New York City healthcare clinic where those guidelines were adopted, we aimed to quantify vaccination responses in HIV+ and HIV- individuals to assess the utility of quantifying antibodies to guide booster timing. Methods Adults who were fully vaccinated against SARS-CoV-2 virus (i.e., 2 Pfizer, 2 Moderna or 1 J&amp;J vaccine) were included if &amp;gt;1 Roche SARS-CoV-2 Semi-Quant Spike Ig Ab test was performed &amp;gt;21 days after vaccination and before any booster (through 03DEC2021). Vaccine response was assessed at the first Ab test and considered adequate (&amp;gt;250 IU/mL) or inadequate (low: ≥51 to ≤250 IU/mL; no response: &amp;lt; 51 IU/mL). The rate of Ab decline was estimated with linear regression, using all sequential Ab tests over the first 6 months between vaccination and boosting. Analyses were stratified by vaccine type, HIV status and CD4 count in HIV+ ( &amp;gt;200 cells/µL cutoff). Results Out of 1979 patients, 869 completed their primary vaccinations, of whom 825 (95%) had ≥1 eligible Ab test (HIV+: 512; HIV-: 313; Table). Overall, 83% had an adequate immune response to vaccination (Pfizer: 82%, Moderna: 94%, J&amp;J: 51%), with similar findings regardless of HIV status and CD4 count (Figure 1). In those with ≥2 Ab tests within six months between vaccination and boosting, Ab levels declined at a rate of 91 IU/mL per month (95% CI: -138, -44). While some variation was observed, rates of Ab decay were generally consistent across vaccine, HIV status and CD4 count strata (Figure 2). Only 1/7 breakthrough COVID-19 infections occurred post booster (6 days later). Conclusion In the pre-omicron era, primary COVID immunization with a mRNA vaccine generally yielded adequate Ab responses, although inadequate responses were observed in 19% of Pfizer, 6% of Moderna, and 49% of J&amp;J vaccine recipients. Ab levels decreased at an average rate of 91 IU/mL per month after primary immunization. Variability in vaccine responses and Ab declines show the utility of measuring spike Ig Ab levels rather than using empiric time frames for booster guidance. Omicron-specific quantitative IgG neutralization levels must be established to inform preventative care. Disclosures Ricky K. Hsu, MD, Gilead: Honoraria|Merck: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Laurence Brunet, PhD, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck &amp; Co: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Jennifer S. Fusco, BS, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck &amp; Co.: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer.

1953. Immune responses, viral shedding, and COVID-19 symptom burden from breakthrough SARS-CoV-2 infection in a 2:1 randomized, double-blind, placebo-controlled Phase 3 study of AZD1222 (ChAdOx1 nCoV-19) vaccination

Abstract Background Breakthrough infections post-COVID-19 vaccination increase with waning immunity and typically produce milder disease than infections in unvaccinated individuals. We investigated immuno-virologic responses and COVID-19 symptom burden upon breakthrough infection in participants from a Phase 3 study of 2-dose primary series AZD1222 vaccination (NCT04516746) to explore disease attenuation. Methods Study participants who experienced protocol-defined COVID-19 symptoms initiated a series of illness visits over 28 days with collection of sera, nasopharyngeal (NP) swabs and saliva samples (SS), and documentation of symptoms (data-cut off: July 30, 2021). For baseline-seronegative participants with PCR-confirmed SARS-CoV-2 infection ≥15 days after dose 2 of AZD1222 or placebo we assessed: anti-SARS-CoV-2 spike (S), nucleocapsid (N) and neutralizing antibody (Ab) titers by multiplex immunoassay and SARS-CoV-2 pseudovirus assay in sera; viral load by quantitative RT-PCR in NP swabs; and viral shedding by qualitative and quantitative RT-PCR in SS. Data were stratified by age and SARS-CoV-2 variant, and time since primary series dose 2. Results Illness Day 1 (ILL-D1) S Ab GMTs in AZD1222 vaccinees were similar to peak GMTs seen 14 days after dose 2 of AZD1222 and were higher vs placebo at all timepoints. The magnitude of S Ab response differed by age: median GMTs were lower at ILL-D1 and higher at ILL-D14 in vaccinees aged ≥65 vs 18–64 years (Fig.1). ILL-D1 overall, SARS-CoV-2 ancestral, alpha, and epsilon variant viral load titers in NP swabs were lower in vaccinees vs placebo (Fig 2). Mean viral load in NP swabs and viral shedding titers in SS were lower in vaccinees vs placebo at all timepoints. Vaccinees reported fewer COVID-19 symptoms than placebo participants, and experienced shorter symptom duration, particularly for fatigue and difficulty breathing. Figure 1. SARS-CoV-2 spike IgG antibody titers upon SARS-CoV-2 infection by participant age in AZD1222 vaccinees and placebo recipients during illness visits Figure 2. Quantification of viral load (nasopharyngeal swabs quantitative viral titer) by SARS-CoV-2 variant at Illness Visit Day 1 Conclusion Improved S Ab responses, lower viral loads, and reduced symptom burden upon breakthrough infection in vaccinees vs placebo recipients, suggest that robust recall responses to AZD1222 vaccination may attenuate COVID-19 disease severity and duration. These findings alongside data on cellular immune responses to breakthrough infection will inform understanding of protective immunity to SARS-CoV-2 infection. Disclosures Magdalena E. Sobieszczyk, MD, MPH, Bill and Melinda Gates Foundation: Grant/Research Support|Gilead Sciences: Grant/Research Support|Janssen Global Services, LLC: Grant/Research Support|Merck: Grant/Research Support|National Institute of Allergy and Infectious Diseases (NIAID): Grant/Research Support|National Institutes of Health (NIH): Grant/Research Support|Sanofi Pasteur Inc.: Grant/Research Support Ann R. Falsey, MD, BioFire Diagnostics: Grant/Research Support|Janssen: Grant/Research Support|Merck, Sharp and Dohme: Grant/Research Support|Novavax: Advisor/Consultant|Pfizer: Grant/Research Support Anne F. Luetkemeyer, MD, AstraZeneca: Grant/Research Support|Gilead Sciences: Grant/Research Support Grant C. Paulsen, MD, AstraZeneca: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Sharon A. Riddler, MD, National Institute of Allergy and Infectious Diseases (NIAID): Grant/Research Support|National Institutes of Health (NIH): Grant/Research Support|Novimmune: Advisor/Consultant Merlin L. Robb, MD, Walter Reed Army Institute of Research: Advisor/Consultant Charlotte-Paige M. Rolle, MD, MPH, Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Janssen: Board Member|ViiV Healthcare: Board Member|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria|Vindico CME: Honoraria Beverly E. Sha, MD, Gilead Sciences: Grant/Research Support|MATEC: Honoraria|University of Chicago: Grant/Research Support|US Government: Grant/Research Support Bahar Ahani, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Anastasia A. Aksyuk, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Himanshu Bansal, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Justin A. Green, MD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Brett Jepson, MS, AstraZeneca: Contractor via Cytel Jill Maaske, MD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Kathryn Shoemaker, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Stephanie Sproule, MMath, AstraZeneca: Contractor via Joule/System One Ann Marie Stanley, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Deidre Wilkins, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Tonya L. Villafana, PhD, MPH, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Elizabeth J. Kelly, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds.

1899. The magnitude and durability of the antibody response to mRNA-based vaccination among SARS-CoV-2 seronegative and seropositive healthcare personnel

Abstract Background Development of robust vaccination guidelines against SARS-CoV-2 requires an understanding of the longitudinal antibody (Ab) response to vaccination and interactions with natural infection. Here, we leveraged an observational cohort study of healthcare personnel (HCP) to study the impact of prior SARS-CoV-2 infection on Ab binding and neutralization after mRNA-based vaccination over a 13 month period. Methods From July 2020 to February 2022, HCP at an academic medical center provided blood samples biweekly for 12 weeks and monthly thereafter. First and second vaccine doses became available in mid-December 2021 and boosters were available starting in October 2021. Individuals were excluded if they did not provide any samples, if baseline serostatus was unknown, and if they received a monoclonal Ab treatment for COVID. ELISA measured total immunoglobulin (Ig) and IgG binding to SARS-CoV-2 RBD. Neutralization was measured by live virus Nanoluc SARS-CoV-2ic assay. Demographics, serostatus, and vaccinations for the total study population and the sub-sample of participants with pre- and post-vaccination antibody measurements. Results Of 213 participants, 192 met inclusion criteria. A majority had detectable IgG levels 8 months after a second dose. Prior to vaccination, median total Ig was higher among seropositive vs. seronegative participants (3.7 vs 1.0, p&amp;lt; 0.001). After a first dose, the median total Ig response was two-fold higher in seropositive compared to seronegative participants (13.8 vs. 7.0, p=0.009). A similar pattern was noted with IgG binding and neutralization. After the second dose, median IgG increased to similar levels in both seropositive and seronegative participants (22.1 vs. 21.2, p=0.8). Neutralization after the second dose was slightly higher in seropositive vs. seronegative participants (log10 3.1 vs. 2.5, p=0.075). Durability of IgG responses after second dose of mRNA-based vaccination against SARS-CoV-2 IgG P/N measurements after 5 days post-V2 for the entire study cohort (incident seropositive: yellow circles, prevalent seropositive (red circles), seronegative (open circles) are shown. The solid lines represent Loess curves for incident and prevalent seropositive participants combined (orange line) and those who were seronegative (grey line). SARS-CoV-2-specific total Ig and IgG subtype responses among healthcare personnel before and after vaccination against SARS-CoV-2 with an mRNA-based vaccine. Total Ig P/N ratios at pre-vaccine, post-V1, post-vaccine 2 (post-V2), and post-booster dose (post-boost) timepoints by serostatus (seronegative: n(-), seropositive: n(+)) are shown in the left panel. For the pre-vaccine time point, the most recent antibody level prior to vaccination (for those who were vaccinated) or most recent antibody level overall (for those who were not vaccinated) is shown. For the post-vaccine time points, the first measurement after 5 days post-vaccination is included. Individuals who were infected with SARS-CoV-2 at any time after the first vaccine dose are shown as open circles with black outlines. The black numbers next to the circles indicate the number of days between vaccination and sample collection for seropositive individuals. SARS-CoV-2 specific IgG P/N ratios respectively at pre-vaccine, post-V1, post-V2, and post-boost timepoints by serostatus (seronegative: n(-), seropositive: n(+)) are shown in the right panel. One individual tested positive for SARS-CoV-2 by PCR shortly after the second vaccine dose (V2); post-V2 results were excluded for this participant. For the pre-vaccine time point, the most recent antibody level prior to vaccination (for those who were vaccinated) or most recent antibody level overall (for those who were not vaccinated) is shown. For the post-vaccine time points, the first measurement after 5 days post-vaccination is included. The dotted line is a P/N ratio of 2.4, the cut-off associated with 99.3% specificity (SARS-CoV-2 IgG-positive above the line, IgG-negative below). Individuals who were infected with SARS-CoV-2 at any time after the first vaccine dose are shown as open circles with black outlines. The black numbers next to the circles indicate the number of days between vaccination and sample collection for seropositive individuals. SARS-CoV-2 D614G live virus neutralization among healthcare personnel by serostatus prior to vaccination. Example neutralization curves are shown in Panel A. Panel B shows the SARS-CoV-2 D614G live virus neutralization titers displayed as EC50 for seropositive (prevalent and incident) individuals and a subset of seronegative individuals. Samples for seronegative individuals were selected by matching on age and time between vaccination and sample collection to the samples from seropositive individuals. Conclusion Antibody responses after SARS-CoV-2 vaccination persist up to 1 year with wide individual variability. Though prior infection was associated with greater Ab responses after a first dose, it did not significantly modify responses after second and third doses. Still, we observed overall slightly higher Ab levels among individuals that had a prior infection before any one of the 3 doses of vaccine. These results suggest that immunity against SARS-CoV-2 prior to vaccination has a role in initial response but does not significantly modify circulating Ab titers after multiple doses of vaccination. Disclosures All Authors: No reported disclosures.

1969. SARS-CoV-2 seroprevalence among patients with cancer and healthcare workers from an oncology referral center during the first year of COVID-19 vaccination in Mexico

Abstract Background Cancer patients (CPs) with COVID-19 have an increased risk of adverse outcomes. In addition, CPs seem to have a lower immune response to SARS-CoV-2 vaccination. This study aimed to evaluate SARS-CoV-2 spike antibodies (anti-S Abs) following COVID-19 vaccination in CPs and healthcare workers (HCWs). Methods We conducted a point-seroprevalence study in CPs and HCWs who received a two-dose scheme with either BNT162b2, AZD1222, or Sputnik-V vaccine. We measured anti-S Abs by quantitative immunoassay to assess humoral immune response. Besides, we quantified anti-nucleocapsid antibodies in a subgroup of individuals to determine prior infection. We compared anti-S Abs titers in both groups and stratified by vaccine type, prior infection, and clinical characteristics. We conducted a multivariate logistic regression to determine variables associated with a poor humoral response. Results Six hundred forty-one individuals were included: 174 (27%) CPs and 467 (73%) HCWs. The median anti-S Abs titter was higher among HCWs compared to CPs (2568 U/mL vs. 1807 U/mL, p=0.002). Both CPs and HCWs with prior infection had higher anti-S Abs titter (p&amp;lt; 0.001). Regardless of the time since vaccination, a higher proportion of subjects with titers &amp;lt; 250 U/mL was observed in CPs (p&amp;lt; 0.001) (Fig 2). In the multivariate analysis, older age (p=0.036), AZD1222 (p=0.003), and Sputnik-V (p=0.020) were associated with lower humoral response among the entire cohort. SARS-CoV-2 spike antibody titers among cancer patients and healthcare workers. Global differences in anti-S Abs titers between CPs and HCWs groups (a) and antibody titers in CPs and HCWs groups stratified by type of received vaccine (b). Abbreviations: CP: Cancer patients, HCW: Healthcare workers. SARS-CoV-2 spike antibody titers according to time since vaccination among cancer patients and healthcare workers. Abbreviations: CP: Cancer patients, HCW: Healthcare workers. Conclusion In this study, both CPs and HCWs showed an adequate response to vaccination; however, CPs had lower anti-S Abs titers and a faster decline over time. Based on our results, new strategies should be assessed to sustain the humoral response to vaccination and thus decrease the COVID-19 burden among the oncologic population. Disclosures All Authors: No reported disclosures.

Memory B Cells and Memory T Cells Induced by SARS-CoV-2 Booster Vaccination or Infection Show Different Dynamics and Responsiveness to the Omicron Variant.

Although the immunological memory produced by BNT162b2 vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been well studied and established, further information using different racial cohorts is necessary to understand the overall immunological response to vaccination. We evaluated memory B and T cell responses to the severe acute respiratory syndrome coronavirus 2 spike protein before and after the third booster using a Japanese cohort. Although the Ab titer against the spike receptor-binding domain (RBD) decreased significantly 8 mo after the second vaccination, the number of memory B cells continued to increase, whereas the number of memory T cells decreased slowly. Memory B and T cells from unvaccinated infected patients showed similar kinetics. After the third vaccination, the Ab titer increased to the level of the second vaccination, and memory B cells increased at significantly higher levels before the booster, whereas memory T cells recovered close to the second vaccination levels. In memory T cells, the frequency of CXCR5+CXCR3+CCR6- circulating follicular Th1 was positively correlated with RBD-specific Ab-secreting B cells. For the response to variant RBDs, although 60-80% of memory B cells could bind to the omicron RBD, their avidity was low, whereas memory T cells show an equal response to the omicron spike. Thus, the persistent presence of memory B and T cells will quickly upregulate Ab production and T cell responses after omicron strain infection, which prevents severe illness and death due to coronavirus disease 2019.

Six Months Follow-Up Study on Health Care Workers on Persistence of Antibodies to SARS-CoV-2 after Covishield Vaccination

BACKGROUND&#x0D; Efficacy of COVID vaccines has been evaluated in various studies. The interim analysis from four randomized controlled trials in UK, Brazil, and south Africa regarding efficacy of two doses of the vaccine was found to be 70.4% (95·8% CI 54·8–80·6). There is a limited data on follow-up Ab titer post vaccination. Hence, the current study is first of its kind with the objective to determine vaccine long term efficacy and its determinants.&#x0D; METHODS&#x0D; Health Care Workers (HCW) from Apollo Multispeciality Hospitals, Kolkata who underwent Covishield vaccination from January 2021 to April 2021 were included in the study. Serological testing was done prior to first and second dose of vaccinations, and additionally around six months post second dose.&#x0D; RESULTS&#x0D; Between January 2021 to April 2021, 2032 HCW, with predominant age of less than 30 years (44.83%) and male gender (61.96%) undergoing Covishield vaccination were enrolled. Antibodies were detected in 953 (46.9%) individuals prior to first dose, 1449 out of 1495 (96.9%) remained positive prior to second dose and 465 out of 504 (92.3%) HCW after 6 months and remaining 39 (7.7%) either had lost or never had antibodies in their blood. The mean ± SD value of first, second and third antibodies were 2.35 ± 3.10, 10.46 ± 4.84 and 8.75 ± 4.88 respectively.&#x0D; CONCLUSIONS&#x0D; This study provides long observation period, covering the complete progress of the pandemic which provides a “real-life” picture of the antibody level dynamics over time, and after vaccination.

Low Spike Antibody Levels and Impaired BA.4/5 Neutralization in Patients with Multiple Myeloma or Waldenstrom’s Macroglobulinemia after BNT162b2 Booster Vaccination

Patients with symptomatic monoclonal gammopathies have impaired humoral responses to COVID-19 vaccination. Their ability to recognize SARS-CoV-2 Omicron variants is of concern. We compared the response to BNT162b2 mRNA vaccinations of patients with multiple myeloma (MM, n = 60) or Waldenstrom's macroglobulinemia (WM, n = 20) with healthy vaccine recipients (n = 37). Patient cohorts on active therapy affecting B cell development had impaired binding and neutralizing antibody (NAb) response rate and magnitude, including several patients lacking responses, even after a 3rd vaccine dose, whereas non-B cell depleting therapies had a lesser effect. In contrast, MM and WM cohorts off-therapy showed increased NAb with a broad response range. ELISA Spike-Receptor Binding Domain (RBD) Ab titers in healthy vaccine recipients and patient cohorts were good predictors of the ability to neutralize not only the original WA1 but also the most divergent Omicron variants BA.4/5. Compared to WA1, significantly lower NAb responses to BA.4/5 were found in all patient cohorts on-therapy. In contrast, the MM and WM cohorts off-therapy showed a higher probability to neutralize BA.4/5 after the 3rd vaccination. Overall, the boost in NAb after the 3rd dose suggests that repeat vaccination of MM and WM patients is beneficial even under active therapy.