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Article: Study of Face Mask-associated Dry Eye among Medical Students.

Gupta, Priyanka / Bansal, Aditi / Aggarwal, Anupriya / Singla, Ritesh

International journal of applied & basic medical research

2023 Volume 13, Issue 4, Page(s) 240–245

Abstract: Purpose: The purpose of this study was to evaluate face mask-associated factors causing dry eye among medical students.: Methodology: This was a cross-sectional study conducted on undergraduate medical and dental students, of all phases, while they ... ...

Abstract	Purpose: The purpose of this study was to evaluate face mask-associated factors causing dry eye among medical students. Methodology: This was a cross-sectional study conducted on undergraduate medical and dental students, of all phases, while they were attending offline classes and were required to wear face masks in accordance with the government regulations. Sociodemographic data, ocular and medical history, face mask-wearing practices, screen usage, and quantification of symptoms using the modified Ocular Surface Disease Index (OSDI) questionnaire were collected. Objective tests were conducted in students having dry eye. The association of quantitative variables was done using ANOVA, Mann-Whitney, and Kruskal-Wallis test, whereas the Chi-square test was done for qualitative variables. Multivariate logistic regression was used to identify the risk factors for varying severity of dry eye. Results: The mean age of the 410 students was 21 ± 1.6 years. According to the OSDI, 39.51% (162/410) of students had dry eyes, 23.41% (96/410) had mild dry eye, 8.78% (36/410) had moderate dry eye, and 7.32% (30/410) had severe dry eye. Face mask-associated factors which were significantly linked to dry eye were N95 masks, loose-fit masks, and 6-8 h of continuous mask use. The Schirmer's test and tear film break-up time were performed on 29 and 20 students, respectively, mean values being 19.25 ± 5.29 mm and 10.15 ± 1.41 s for nonsevere and 6.53 ± 1.55 mm and 5.3 ± 0.98 s for severe dry eye, respectively. Conclusion: It is important to educate medical students and create awareness regarding "face mask-appropriate behavior" to reduce the chances of dry eye secondary to face masks use.
Language	English
Publishing date	2023-12-08
Publishing country	India
Document type	Journal Article
ZDB-ID	2645750-7
ISSN	2248-9606 ; 2229-516X
ISSN (online)	2248-9606
ISSN	2229-516X
DOI	10.4103/ijabmr.ijabmr_366_23
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Atypical Asymmetric Presentation of Severe Graves' Orbitopathy.

Gupta, Priyanka / Kaur, Navdeep / Goyal, Aman / Aggarwal, Anupriya

Cureus

2023 Volume 15, Issue 9, Page(s) e45907

Abstract: Graves' disease is a self-limiting autoimmune thyroid disorder caused by stimulating antibodies to the thyroid-stimulating hormone receptor. It usually affects middle-aged females in the fourth to sixth decade of life. It is distinguished by keratopathy, ...

Abstract	Graves' disease is a self-limiting autoimmune thyroid disorder caused by stimulating antibodies to the thyroid-stimulating hormone receptor. It usually affects middle-aged females in the fourth to sixth decade of life. It is distinguished by keratopathy, chemosis, proptosis, and eyelid swelling, in addition to ocular discomfort. A total of 3-5% of cases present with a severe form of Graves' orbitopathy, which manifests with diminution of vision, optic nerve compression, optic neuropathy, and exposure keratopathy. We describe a case of a 34-year-old female patient who presented with the chief complaint of rapid deterioration of vision over a period of three months in the right eye. Ocular examination revealed proptosis, widened palpebral aperture, elevation of intra-ocular pressure (IOP) in the upgaze, restricted eye movements, and signs of optic nerve compression. Findings were confirmed on a CT scan of the orbit. The unusual presentation in this case was that she had rapid, significant deterioration of vision in the right eye, with a progression of proptosis more marked in the contralateral eye. This underlies the importance of thoroughly examining for any possible orbital apex syndrome in both eyes, not just the eye with marked proptosis. The patient, being reluctant for orbital decompression, was prescribed IV methylprednisolone 1 g for three consecutive days, which reduced her proptosis and improved her vision. This acted as a temporary measure to increase the duration of the surgical window until the time the patient undergoes the surgery.
Language	English
Publishing date	2023-09-25
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.45907
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Article: Embedding of HIV Egress within Cortical F-Actin

Aggarwal, Anupriya / Stella, Alberto Ospina / Henry, Catherine C. / Narayan, Kedar / Turville, Stuart G.

Pathogens. 2022 Jan. 03, v. 11, no. 1

2022

Abstract: F-Actin remodeling is important for the spread of HIV via cell–cell contacts; however, the mechanisms by which HIV corrupts the actin cytoskeleton are poorly understood. Through live cell imaging and focused ion beam scanning electron microscopy (FIB-SEM) ...

Abstract	F-Actin remodeling is important for the spread of HIV via cell–cell contacts; however, the mechanisms by which HIV corrupts the actin cytoskeleton are poorly understood. Through live cell imaging and focused ion beam scanning electron microscopy (FIB-SEM), we observed F-Actin structures that exhibit strong positive curvature to be enriched for HIV buds. Virion proteomics, gene silencing, and viral mutagenesis supported a Cdc42-IQGAP1-Arp2/3 pathway as the primary intersection of HIV budding, membrane curvature and F-Actin regulation. Whilst HIV egress activated the Cdc42-Arp2/3 filopodial pathway, this came at the expense of cell-free viral release. Importantly, release could be rescued by cell–cell contact, provided Cdc42 and IQGAP1 were present. From these observations, we conclude that a proportion out-going HIV has corrupted a central F-Actin node that enables initial coupling of HIV buds to cortical F-Actin to place HIV at the leading cell edge. Whilst this initially prevents particle release, the maturation of cell–cell contacts signals back to this F-Actin node to enable viral release & subsequent infection of the contacting cell.
Keywords	actin ; genes ; microfilaments ; mutagenesis ; proteomics ; virion
Language	English
Dates of publication	2022-0103
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11010056
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Article: Embedding of HIV Egress within Cortical F-Actin.

Aggarwal, Anupriya / Stella, Alberto Ospina / Henry, Catherine C / Narayan, Kedar / Turville, Stuart G

Pathogens (Basel, Switzerland)

2022 Volume 11, Issue 1

Abstract: F-Actin remodeling is important for the spread of HIV via cell-cell contacts; however, the mechanisms by which HIV corrupts the actin cytoskeleton are poorly understood. Through live cell imaging and focused ion beam scanning electron microscopy (FIB-SEM) ...

Abstract	F-Actin remodeling is important for the spread of HIV via cell-cell contacts; however, the mechanisms by which HIV corrupts the actin cytoskeleton are poorly understood. Through live cell imaging and focused ion beam scanning electron microscopy (FIB-SEM), we observed F-Actin structures that exhibit strong positive curvature to be enriched for HIV buds. Virion proteomics, gene silencing, and viral mutagenesis supported a Cdc42-IQGAP1-Arp2/3 pathway as the primary intersection of HIV budding, membrane curvature and F-Actin regulation. Whilst HIV egress activated the Cdc42-Arp2/3 filopodial pathway, this came at the expense of cell-free viral release. Importantly, release could be rescued by cell-cell contact, provided Cdc42 and IQGAP1 were present. From these observations, we conclude that a proportion out-going HIV has corrupted a central F-Actin node that enables initial coupling of HIV buds to cortical F-Actin to place HIV at the leading cell edge. Whilst this initially prevents particle release, the maturation of cell-cell contacts signals back to this F-Actin node to enable viral release & subsequent infection of the contacting cell.
Language	English
Publishing date	2022-01-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11010056
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Article ; Online: Layer-by-Layer Particles Deliver Epigenetic Silencing siRNA to HIV-1 Latent Reservoir Cell Types.

Czuba-Wojnilowicz, Ewa / Klemm, Vera / Cortez-Jugo, Christina / Turville, Stuart / Aggarwal, Anupriya / Caruso, Frank / Kelleher, Anthony D / Ahlenstiel, Chantelle L

Molecular pharmaceutics

2023 Volume 20, Issue 4, Page(s) 2039–2052

Abstract: For over two decades, nanomaterials have been employed to facilitate intracellular delivery of small interfering RNA (siRNA), both in vitro and in vivo, to induce post-transcriptional gene silencing (PTGS) via RNA interference. Besides PTGS, siRNAs are ... ...

Abstract	For over two decades, nanomaterials have been employed to facilitate intracellular delivery of small interfering RNA (siRNA), both in vitro and in vivo, to induce post-transcriptional gene silencing (PTGS) via RNA interference. Besides PTGS, siRNAs are also capable of transcriptional gene silencing (TGS) or epigenetic silencing, which targets the gene promoter in the nucleus and prevents transcription via repressive epigenetic modifications. However, silencing efficiency is hampered by poor intracellular and nuclear delivery. Here, polyarginine-terminated multilayered particles are reported as a versatile system for the delivery of TGS-inducing siRNA to potently suppress virus transcription in HIV-infected cells. siRNA is complexed with multilayered particles formed by layer-by-layer assembly of poly(styrenesulfonate) and poly(arginine) and incubated with HIV-infected cell types, including primary cells. Using deconvolution microscopy, uptake of fluorescently labeled siRNA is observed in the nuclei of HIV-1 infected cells. Viral RNA and protein are measured to confirm functional virus silencing from siRNA delivered using particles 16 days post-treatment. This work extends conventional particle-enabled PTGS siRNA delivery to the TGS pathway and paves the way for future studies on particle-delivered siRNA for efficient TGS of various diseases and infections, including HIV.
MeSH term(s)	Humans ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; HIV-1/genetics ; HIV-1/metabolism ; Gene Silencing ; RNA Interference ; Epigenesis, Genetic/genetics ; HIV Infections/genetics ; HIV Infections/therapy
Chemical Substances	RNA, Small Interfering
Language	English
Publishing date	2023-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/acs.molpharmaceut.2c01030
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Article ; Online: Virtual screening and in vitro validation of natural compound inhibitors against SARS-CoV-2 spike protein.

Power, Helen / Wu, Jiadai / Turville, Stuart / Aggarwal, Anupriya / Valtchev, Peter / Schindeler, Aaron / Dehghani, Fariba

Bioorganic chemistry

2021 Volume 119, Page(s) 105574

Abstract: The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to a major public health burden and has resulted in millions of deaths worldwide. As effective treatments are limited, there is a significant requirement for high-throughput, low resource ... ...

Abstract	The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to a major public health burden and has resulted in millions of deaths worldwide. As effective treatments are limited, there is a significant requirement for high-throughput, low resource methods for the discovery of novel antivirals. The SARS-CoV-2 spike protein plays a key role in viral entry and has been identified as a therapeutic target. Using the available spike crystal structure, we performed a virtual screen with a library of 527 209 natural compounds against the receptor binding domain of this protein. Top hits from this screen were subjected to a second, more comprehensive molecular docking experiment and filtered for favourable ADMET properties. The in vitro activity of 10 highly ranked compounds was assessed using a virus neutralisation assay designed to facilitate viral entry in a physiologically relevant manner via the plasma membrane route. Subsequently, four compounds ZINC02111387, ZINC02122196, SN00074072 and ZINC04090608 were identified to possess antiviral activity in the µM range. These findings validate the virtual screening method as a tool for identifying novel antivirals and provide a basis for future drug development against SARS-CoV-2.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Biological Products/pharmacology ; Biological Products/toxicity ; Computer Simulation ; Drug Evaluation, Preclinical ; Humans ; Models, Molecular ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Neutralization Tests ; Reproducibility of Results ; SARS-CoV-2/drug effects ; Spike Glycoprotein, Coronavirus/antagonists & inhibitors ; Virus Internalization/drug effects
Chemical Substances	Antiviral Agents ; Biological Products ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-12-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	120080-x
ISSN	1090-2120 ; 0045-2068
ISSN (online)	1090-2120
ISSN	0045-2068
DOI	10.1016/j.bioorg.2021.105574
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Article ; Online: Enhanced stability of the SARS CoV-2 spike glycoprotein following modification of an alanine cavity in the protein core.

Poumbourios, Pantelis / Langer, Christine / Boo, Irene / Zakir, Tasnim / Center, Rob J / Akerman, Anouschka / Milogiannakis, Vanessa / Aggarwal, Anupriya / Johnstone, Bronte A / Ha, Jungmin / Coulibaly, Fasséli / Turville, Stuart G / Drummer, Heidi E

PLoS pathogens

2023 Volume 19, Issue 5, Page(s) e1010981

Abstract: The spike (S) glycoprotein of SARS CoV-2 is the target of neutralizing antibodies (NAbs) that are crucial for vaccine effectiveness. The S1 subunit binds ACE2 while the S2 subunit mediates virus-cell membrane fusion. S2 is a class I fusion glycoprotein ... ...

Abstract	The spike (S) glycoprotein of SARS CoV-2 is the target of neutralizing antibodies (NAbs) that are crucial for vaccine effectiveness. The S1 subunit binds ACE2 while the S2 subunit mediates virus-cell membrane fusion. S2 is a class I fusion glycoprotein subunit and contains a central coiled coil that acts as a scaffold for the conformational changes associated with fusion function. The coiled coil of S2 is unusual in that the 3-4 repeat of inward-facing positions are mostly occupied by polar residues that mediate few inter-helical contacts in the prefusion trimer. We examined how insertion of bulkier hydrophobic residues (Val, Leu, Ile, Phe) to fill a cavity next to Ala1016 and Ala1020 in the 3-4 repeat affects the stability and antigenicity of S trimers. Substitution of Ala1016 with bulkier hydrophobic residues in the context of a prefusion-stabilized S trimer, S2P-FHA, was associated with increased thermal stability. S glycoprotein membrane fusion function was retained with Ala1016/Ala1020 cavity-filling mutations associated with improved recombinant S2P-FHA thermostability, however 2 mutants, A1016L and A1016V/A1020I, lacked ability to mediate entry of S-HIV-1 pseudoparticles into 293-ACE2 cells. When assessed as immunogens, two thermostable S2P-FHA mutants derived from the ancestral isolate, A1016L (16L) and A1016V/A1020I (VI) elicited neutralizing antibody with 50%-inhibitory dilutions (ID50s) in the range 2,700-5,110 for ancestral and Delta-derived viruses, and 210-1,744 for Omicron BA.1. The antigens elicited antibody specificities directed to the receptor-binding domain (RBD), N-terminal domain (NTD), fusion peptide and stem region of S2. The VI mutation enabled the production of intrinsically stable Omicron BA.1 and Omicron BA.4/5 S2P-FHA-like ectodomain oligomers in the absence of an external trimerization motif (T4 foldon), thus representing an alternative approach for stabilizing oligomeric S glycoprotein vaccines.
MeSH term(s)	Humans ; Spike Glycoprotein, Coronavirus ; Severe Acute Respiratory Syndrome ; Angiotensin-Converting Enzyme 2 ; COVID-19 ; Antibodies, Neutralizing
Chemical Substances	spike protein, SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Antibodies, Neutralizing
Language	English
Publishing date	2023-05-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1010981
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Article: Demographic comparison of the first, second and third waves of COVID-19 in a tertiary care hospital at Jaipur, India.

Singh, Sheetu / Sharma, Arvind / Gupta, Arvind / Joshi, Madhur / Aggarwal, Anupriya / Soni, Nitika / Sana / Jain, Devendra K / Verma, Pankaj / Khandelwal, Deepchand / Singh, Virendra

Lung India : official organ of Indian Chest Society

2023 Volume 39, Issue 6, Page(s) 525–531

Abstract: Background: Coronavirus disease 2019 (COVID-19) infection in India demonstrated three peaks in India, with differences in presentation and outcome in all the three waves. The aim of the paper was to assess differences in the epidemiological, clinical ... ...

Abstract	Background: Coronavirus disease 2019 (COVID-19) infection in India demonstrated three peaks in India, with differences in presentation and outcome in all the three waves. The aim of the paper was to assess differences in the epidemiological, clinical features and outcomes of patients with COVID-19 presenting at a tertiary care hospital in the three waves at Jaipur, India. Methods: This was a retrospective study conducted at a tertiary care hospital at Jaipur, India. Demographic, clinical features and outcomes were compared of confirmed COVID-19 cases admitted during the first wave (16-7-2020 to 31-1-2021), second wave (16-3-2021 to 6-5-2021) and third wave (1-1-22 to 20-2-22) of the outbreak. Results: There were 1006 cases, 639 cases and 125 cases admitted during the three waves, respectively. The cases presenting in the second wave were significantly younger, with significantly higher prevalence of symptoms such as fever, cough, sore throat, nausea, vomiting, headache, muscle ache, loss of appetite and fatigue (P < 0.05). A significantly higher proportion of patients received Remdesivir in the second wave (P < 0.001). However, in the second wave, the use of low molecular weight heparin, plasma therapy, non-invasive and invasive ventilator were higher (P < 0.001). Co-morbid conditions were significantly higher in the admitted patients during the third wave (P < 0.05). Radiological scores were similar in second and third wave, significantly higher than the first wave. Lymphopenia and rise of inflammatory markers including C-reactive protein and interleukin-6 were more evident in the second wave (P < 0.001). The mean mortality, hospital stay and air-leak complications were also significantly higher in the second wave (P < 0.001). Conclusions: The second wave was more vicious in terms of symptoms, inflammatory markers, radiology, complications, requirement of ventilation and mortality. Mutation in the virus, lack of immunity and vaccination at the time point of second wave could have been the possible causes. The ferocity of the second wave has important implications for the government to formulate task forces for effective management of such pandemics.
Language	English
Publishing date	2023-01-09
Publishing country	India
Document type	Journal Article
ZDB-ID	2410801-7
ISSN	0974-598X ; 0970-2113
ISSN (online)	0974-598X
ISSN	0970-2113
DOI	10.4103/lungindia.lungindia_265_22
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Article ; Online: Novel siRNA therapeutics demonstrate multi-variant efficacy against SARS-CoV-2.

Bowden-Reid, Ellen / Ledger, Scott / Zhang, Yuan / Di Giallonardo, Francesca / Aggarwal, Anupriya / Stella, Alberto Ospina / Akerman, Anouschka / Milogiannakis, Vanessa / Walker, Gregory / Rawlinson, William / Turville, Stuart / Kelleher, Anthony D / Ahlenstiel, Chantelle

Antiviral research

2023 Volume 217, Page(s) 105677

Abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that causes COVID-19 disease, with an estimated global mortality of approximately 2%. While global response strategies, which are predominantly reliant on regular ... ...

Abstract	Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that causes COVID-19 disease, with an estimated global mortality of approximately 2%. While global response strategies, which are predominantly reliant on regular vaccinations, have shifted from zero COVID to living with COVID, there is a distinct lack of broad-spectrum direct acting antiviral therapies that maintain efficacy across evolving SARS-CoV-2 variants of concern. This is of most concern for immunocompromised and immunosuppressed individuals who lack robust immune responses following vaccination, and others at risk for severe COVID and long-COVID. RNA interference (RNAi) therapeutics induced by short interfering RNAs (siRNAs) offer a promising antiviral treatment option, with broad-spectrum antiviral capabilities unparalleled by current antiviral therapeutics and a high genetic barrier to antiviral escape. Here we describe novel siRNAs, targeting highly conserved regions of the SARS-CoV-1 and 2 genome of both human and animal species, with multi-variant antiviral potency against eight SARS-CoV-2 lineages - Ancestral VIC01, Alpha, Beta, Gamma, Delta, Zeta, Kappa and Omicron. Treatment with our siRNA resulted in significant protection against virus-mediated cell death in vitro, with >97% cell survival (P < 0.0001), and corresponding reductions of viral nucleocapsid RNA of up to 99.9% (P < 0.0001). When compared to antivirals; Sotrovimab and Remdesivir, the siRNAs demonstrated a more potent antiviral effect and similarly, when multiplexing siRNAs to target different viral regions simultaneously, an increased antiviral effect was observed compared to individual siRNA treatments (P < 0.0001). These results demonstrate the potential for a highly effective broad-spectrum direct acting antiviral against multiple SARS-CoV-2 variants, including variants resistant to antivirals and vaccine generated neutralizing antibodies.
MeSH term(s)	Animals ; Humans ; RNA, Small Interfering/genetics ; SARS-CoV-2/genetics ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Post-Acute COVID-19 Syndrome ; COVID-19/therapy ; Hepatitis C, Chronic ; Antibodies, Neutralizing/therapeutic use ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus
Chemical Substances	RNA, Small Interfering ; Antiviral Agents ; Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-07-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2023.105677
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Article ; Online: Immunoglobulin repertoire restriction characterizes the serological responses of patients with predominantly antibody deficiency.

Troelnikov, Alexander / Armour, Bridie / Putty, Trishni / Aggarwal, Anupriya / Akerman, Anouschka / Milogiannakis, Vanessa / Chataway, Tim / King, Jovanka / Turville, Stuart G / Gordon, Tom P / Wang, Jing Jing

The Journal of allergy and clinical immunology

2023 Volume 152, Issue 1, Page(s) 290–301.e7

Abstract: Background: Predominantly antibody deficiency (PAD) is the most common category of inborn errors of immunity and is underpinned by impaired generation of appropriate antibody diversity and quantity. In the clinic, responses are interrogated by ... ...

Abstract	Background: Predominantly antibody deficiency (PAD) is the most common category of inborn errors of immunity and is underpinned by impaired generation of appropriate antibody diversity and quantity. In the clinic, responses are interrogated by assessment of vaccination responses, which is central to many PAD diagnoses. However, the composition of the generated antibody repertoire is concealed from traditional quantitative measures of serological responses. Leveraging modern mass spectrometry-based proteomics (MS-proteomics), it is possible to elaborate the molecular features of specific antibody repertoires, which may address current limitations of diagnostic vaccinology. Objectives: We sought to evaluate serum antibody responses in patients with PAD following vaccination with a neo-antigen (severe acute respiratory syndrome coronavirus-2 vaccination) using MS-proteomics. Methods: Following severe acute respiratory syndrome coronavirus-2 vaccination, serological responses in individuals with PAD and healthy controls (HCs) were assessed by anti-S1 subunit ELISA and neutralization assays. Purified anti-S1 subunit IgG and IgM was profiled by MS-proteomics for IGHV subfamily usage and somatic hypermutation analysis. Results: Twelve patients with PAD who were vaccine-responsive were recruited with 11 matched vaccinated HCs. Neutralization and end point anti-S1 titers were lower in PAD. All subjects with PAD demonstrated restricted anti-S1 IgG antibody repertoires, with usage of <5 IGHV subfamilies (median: 3; range 2-4), compared to ≥5 for the 11 HC subjects (P < .001). IGHV3-7 utilization was far less common in patients with PAD than in HCs (2 of 12 vs 10 of 11; P = .001). Amino acid substitutions due to somatic hypermutation per subfamily did not differ between groups. Anti-S1 IgM was present in 64% and 50% of HC and PAD cohorts, respectively, and did not differ significantly between HCs and patients with PAD. Conclusions: This study demonstrates the breadth of anti-S1 antibodies elicited by vaccination at the proteome level and identifies stereotypical restriction of IGHV utilization in the IgG repertoire in patients with PAD compared with HC subjects. Despite uniformly pauci-clonal antibody repertoires some patients with PAD generated potent serological responses, highlighting a possible limitation of traditional serological techniques. These findings suggest that IgG repertoire restriction is a key feature of antibody repertoires in PAD.
MeSH term(s)	Humans ; COVID-19 ; Amino Acid Substitution ; Biological Assay ; Primary Immunodeficiency Diseases ; Vaccination ; Immunoglobulin G ; Immunoglobulin M ; Antibodies, Viral
Chemical Substances	Immunoglobulin G ; Immunoglobulin M ; Antibodies, Viral
Language	English
Publishing date	2023-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2023.02.033
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