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1.
Iran J Allergy Asthma Immunol ; 23(2): 158-167, 2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38822511

ABSTRACT

Patients with inborn errors of immunity (IEI) are among the high-risk groups regarding COVID-19. Receiving booster doses (third and fourth) in addition to the standard doses is recommended in these patients. This study investigated the antibody response before and after a booster dose of Sinopharm vaccine in IEI patients.  Thirty patients (>12 years) with antibody deficiencies, referred to Imam Khomeini Hospital and Children's Medical Center in Tehran, were enrolled in this prospective cross-sectional study. All patients were fully vaccinated with the BBIBP-CorV vaccine (2 doses of Sinopharm). Initial measurements of anti-receptor-binding domain (anti-RBD) and anti-nucleocapsid (anti-N) IgG antibody responses were conducted by enzyme-linked immunosorbent assay (ELISA). Subsequently, all patients received a booster dose of the vaccine. Four to six weeks after booster injection, the levels of antibodies were re-evaluated.  Twenty patients with common variable immunodeficiency (CVID), 7 cases with agammaglobulinemia and 3 patients with hyper IgM syndrome were studied. Anti-RBD IgG and anti-N IgG antibodies increased in all patients after the booster. Our results indicated the need of receiving booster doses of the COVID-19 vaccine in patients with antibody deficiencies, even for enhancing humoral immune response specially in patients with CVID.


Subject(s)
Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunization, Secondary , Immunoglobulin G , SARS-CoV-2 , Humans , Male , COVID-19/immunology , COVID-19/prevention & control , Female , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , SARS-CoV-2/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Adult , Immunoglobulin G/blood , Immunoglobulin G/immunology , Cross-Sectional Studies , Adolescent , Iran , Prospective Studies , Antibody Formation/immunology , Vaccines, Inactivated/immunology , Vaccines, Inactivated/administration & dosage , Child , Middle Aged , Young Adult
2.
Appl Microbiol Biotechnol ; 108(1): 355, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822832

ABSTRACT

Getah virus (GETV) is a re-emerging mosquito-borne alphavirus that is highly pathogenic, mainly to pigs and horses. There are no vaccines or treatments available for GETV in swine in China. Therefore, the development of a simple, rapid, specific, and sensitive serological assay for GETV antibodies is essential for the prevention and control of GETV. Current antibody monitoring methods are time-consuming, expensive, and dependent on specialized instrumentation, and these features are not conducive to rapid detection in clinical samples. To address these problem, we developed immunochromatographic test strips (ICTS) using eukaryotically expressed soluble recombinant p62-E1 protein of GETV as a labelled antigen, which has good detection sensitivity and no cross-reactivity with other common porcine virus-positive sera. The ICTS is highly compatible with IFA and ELISA and can be stored for 1 month at 37 °C and for at least 3 months at room temperature. Hence, p62-E1-based ICTS is a rapid, accurate, and convenient method for rapid on-site detection of GETV antibodies. KEY POINTS: • We established a rapid antibody detection method that can monitor GETV infection • We developed colloidal gold test strips with high sensitivity and specificity • The development of colloidal gold test strips will aid in the field serologic detection of GETV.


Subject(s)
Alphavirus , Antibodies, Viral , Gold Colloid , Sensitivity and Specificity , Animals , Gold Colloid/chemistry , Antibodies, Viral/blood , Antibodies, Viral/immunology , Alphavirus/immunology , Swine , Chromatography, Affinity/methods , Alphavirus Infections/diagnosis , Alphavirus Infections/immunology , Swine Diseases/diagnosis , Swine Diseases/virology , Reagent Strips , China , Enzyme-Linked Immunosorbent Assay/methods
3.
Nat Commun ; 15(1): 4488, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802350

ABSTRACT

Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and environmental fomites of 77 acute MPXV infections (HIV co-infection: N = 42) were collected every two to three days and used for detection of MPXV DNA, surface protein specific antibodies and neutralizing titers. Skin lesions show 100% positivity rate of MPXV DNA, followed by rectum (88.16%), saliva (83.78%) and oropharynx (78.95%). Positivity rate of oropharynx decreases rapidly after 7 days post symptom onset (d.p.o), while the rectum and saliva maintain a positivity rate similar to skin lesions. Viral dynamics are similar among skin lesions, saliva and oropharynx, with a peak at about 6 d.p.o. In contrast, viral levels in the rectum peak at the beginning of symptom onset and decrease rapidly thereafter. 52.66% of environmental fomite swabs are positive for MPXV DNA, with highest positivity rate (69.89%) from air-conditioning air outlets. High seropositivity against A29L (100%) and H3L (94.74%) are detected, while a correlation between IgG endpoint titers and neutralizing titers is only found for A29L. Most indexes are similar between HIV and Non-HIV participants, while HIV and rectitis are associated with higher viral loads in rectum.


Subject(s)
Antibodies, Viral , Monkeypox virus , Mpox (monkeypox) , Virus Shedding , Humans , Male , Antibodies, Viral/immunology , Antibodies, Viral/blood , Prospective Studies , Adult , Monkeypox virus/immunology , Mpox (monkeypox)/immunology , Mpox (monkeypox)/virology , Mpox (monkeypox)/epidemiology , Saliva/virology , Saliva/immunology , HIV Infections/immunology , HIV Infections/virology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Middle Aged , Longitudinal Studies , DNA, Viral , Oropharynx/virology , Oropharynx/immunology , Coinfection/immunology , Coinfection/virology , Coinfection/epidemiology , Viral Load , Fomites/virology
4.
Nat Commun ; 15(1): 4505, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802413

ABSTRACT

Avian influenza A virus H7N9 causes severe human infections with >30% fatality. Currently, there is no H7N9-specific prevention or treatment for humans. Here, from a 2013 H7N9 convalescent case in Hong Kong, we isolate four hemagglutinin (HA)-reactive monoclonal antibodies (mAbs), with three directed to the globular head domain (HA1) and one to the stalk domain (HA2). Two clonally related HA1-directed mAbs, H7.HK1 and H7.HK2, potently neutralize H7N9 and protect female mice from lethal H7N9/AH1 challenge. Cryo-EM structures reveal that H7.HK1 and H7.HK2 bind to a ß14-centered surface and disrupt the 220-loop that makes hydrophobic contacts with sialic acid on an adjacent protomer, thereby blocking viral entry. Sequence analysis indicates the lateral patch targeted by H7.HK1 and H7.HK2 to be conserved among influenza subtypes. Both H7.HK1 and H7.HK2 retain HA1 binding and neutralization capacity to later H7N9 isolates from 2016-2017, consistent with structural data showing that the antigenic mutations during this timeframe occur at their epitope peripheries. The HA2-directed mAb H7.HK4 lacks neutralizing activity but when used in combination with H7.HK2 moderately augments female mouse protection. Overall, our data reveal antibodies to a conserved lateral HA1 supersite that confer neutralization, and when combined with a HA2-directed non-neutralizing mAb, augment protection.


Subject(s)
Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , Hemagglutinin Glycoproteins, Influenza Virus , Influenza A Virus, H7N9 Subtype , Influenza, Human , Influenza A Virus, H7N9 Subtype/immunology , Animals , Antibodies, Neutralizing/immunology , Humans , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Female , Influenza, Human/immunology , Influenza, Human/virology , Influenza, Human/prevention & control , Mice , Antibodies, Viral/immunology , Antibodies, Monoclonal/immunology , Mice, Inbred BALB C , Cryoelectron Microscopy , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/prevention & control , Orthomyxoviridae Infections/virology , Epitopes/immunology
5.
Sci Rep ; 14(1): 12176, 2024 05 28.
Article in English | MEDLINE | ID: mdl-38806644

ABSTRACT

Although the mRNA SARS-CoV-2 vaccine has improved the mortality rate in the general population, its efficacy against rapidly mutating virus strains, especially in kidney transplant recipients, remains unclear. We examined the anti-SARS-CoV-2 spike protein IgG antibody and neutralizing antibody titers and cellular immunity against B.1.1, BA.1, and BA.5 antigens in 73 uninfected kidney recipients and 16 uninfected healthy controls who received three doses of an mRNA SARS-CoV-2 vaccine. The IgG antibody titers were significantly lower in recipients than in healthy controls. Similarly, neutralizing antibody titers against three viral variants were significantly lower in recipients. When the virus was mutated, the neutralizing antibody titers decreased significantly in both groups. In cellular immunity analysis, the number of spike-specific CD8 + non-naïve T cells against three variants significantly decreased in recipients. Conversely, the frequency of spike-specific Th2 CD4 + T-cells in recipients was higher than that in healthy controls. Nineteen recipients and six healthy controls also received a bivalent omicron-containing booster vaccine, leading to increase IgG and neutralizing antibody titers in both groups. After that, eleven recipients and five healthy controls received XBB.1.5 monovalent vaccines, increasing the neutralizing antibody titers against not only XBB.1.5, but also EG.5.1 and BA.2.86 antigens in kidney recipients. Although kidney recipients did not gain sufficient immunity against Omicron BA.5 with the third dose of vaccine, humoral response against mutant SARS-CoV-2 lineages significantly increased after bivalent Omicron-containing booster vaccine and the XBB.1.5 monovalent vaccine. Therefore, it is important for kidney recipients to continue to administer updated vaccines.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunoglobulin G , Kidney Transplantation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Kidney Transplantation/adverse effects , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Female , Male , Middle Aged , Antibodies, Viral/immunology , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , Adult , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunity, Cellular , Vaccination/methods , Transplant Recipients , Aged , Immunization, Secondary
6.
BMC Infect Dis ; 24(1): 535, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38807038

ABSTRACT

BACKGROUND: To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV, wIPV). METHODS: A cross-sectional investigation was conducted at four sites in Chongqing, China, healthy infants aged 60-89 days were conveniently recruited and divided into four groups according to their received primary polio vaccination schedules (2sIPV + bOPV, 2wIPV + bOPV, 3sIPV, and 3wIPV). The sero-protection and neutralizing antibody titers against poliovirus serotypes (type 1, 2, and 3) were compared after the last dose. RESULTS: There were 408 infants completed the protocol. The observed seropositivity was more than 96% against poliovirus types 1, 2, and 3 in all groups. IPV-only groups induced higher antibody titers(GMT) against poliovirus type 2 (Median:192, QR: 96-384, P<0.05) than the "2IPV + bOPV" group. While the "2IPV + bOPV" group induced significantly higher antibody titers against poliovirus type 1 (Median:2048, QR: 768-2048, P<0.05)and type 3 (Median:2048, QR: 512-2048, P<0.05) than the IPV-only group. CONCLUSIONS: Our findings have proved that the two doses of IPV with one dose of bOPV is currently the best polio routine immunization schedule in China.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Immunization Schedule , Poliomyelitis , Poliovirus Vaccine, Inactivated , Poliovirus Vaccine, Oral , Poliovirus , Humans , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Poliomyelitis/prevention & control , Poliomyelitis/immunology , Infant , Poliovirus Vaccine, Oral/immunology , Poliovirus Vaccine, Oral/administration & dosage , Male , Female , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cross-Sectional Studies , China , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Poliovirus/immunology , Immunogenicity, Vaccine , Vaccination
7.
J Nanobiotechnology ; 22(1): 295, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38807131

ABSTRACT

The signal sequence played a crucial role in the efficacy of mRNA vaccines against virus pandemic by influencing antigen translation. However, limited research had been conducted to compare and analyze the specific mechanisms involved. In this study, a novel approach was introduced by substituting the signal sequence of the mRNA antigen to enhance its immune response. Computational simulations demonstrated that various signal peptides differed in their binding capacities with the signal recognition particle (SRP) 54 M subunit, which positively correlated with antigen translation efficiency. Our data revealed that the signal sequences of tPA and IL-6-modified receptor binding domain (RBD) mRNA vaccines sequentially led to higher antigen expression and elicited more robust humoral and cellular immune protection against the SARS-CoV-2 compared to the original signal sequence. By highlighting the importance of the signal sequence, this research provided a foundational and safe approach for ongoing modifications in signal sequence-antigen design, aiming to optimize the efficacy of mRNA vaccines.


Subject(s)
Protein Sorting Signals , SARS-CoV-2 , mRNA Vaccines , Animals , Mice , SARS-CoV-2/immunology , COVID-19/prevention & control , COVID-19/immunology , Mice, Inbred BALB C , RNA, Messenger/genetics , COVID-19 Vaccines/immunology , Female , Humans , Antigens, Viral/immunology , Antigens, Viral/genetics , Antigens, Viral/chemistry , Antibodies, Viral/immunology , Immunity, Humoral , Vaccines, Synthetic/immunology , Immunity, Cellular
8.
JCI Insight ; 9(10)2024 May 22.
Article in English | MEDLINE | ID: mdl-38775156

ABSTRACT

Since its emergence, SARS-CoV-2 has been continuously evolving, hampering the effectiveness of current vaccines against COVID-19. mAbs can be used to treat patients at risk of severe COVID-19. Thus, the development of broadly protective mAbs and an understanding of the underlying protective mechanisms are of great importance. Here, we isolated mAbs from donors with breakthrough infection with Omicron subvariants using a single-B cell screening platform. We identified a mAb, O5C2, which possesses broad-spectrum neutralization and antibody-dependent cell-mediated cytotoxic activities against SARS-CoV-2 variants, including EG.5.1. Single-particle analysis by cryo-electron microscopy revealed that O5C2 targeted an unusually large epitope within the receptor-binding domain of spike protein that overlapped with the angiotensin-converting enzyme 2 binding interface. Furthermore, O5C2 effectively protected against BA.5 Omicron infection in vivo by mediating changes in transcriptomes enriched in genes involved in apoptosis and interferon responses. Our findings provide insights into the development of pan-protective mAbs against SARS-CoV-2.


Subject(s)
Antibodies, Viral , COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , SARS-CoV-2/immunology , Humans , COVID-19/immunology , COVID-19/virology , Antibodies, Viral/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Animals , Mice , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/immunology , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Cryoelectron Microscopy , Epitopes/immunology , Broadly Neutralizing Antibodies/immunology , Antibody-Dependent Cell Cytotoxicity/immunology , Female
9.
Emerg Microbes Infect ; 13(1): 2359004, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38779718

ABSTRACT

As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions (Δ15-26 and Δ136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Immune Evasion , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , COVID-19/virology , COVID-19/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibodies, Viral/blood , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Cell Line , Mutation , Neutralization Tests
10.
Emerg Infect Dis ; 30(6): 1267-1270, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38782366

ABSTRACT

We assessed SARS-CoV-2 seroprevalence in Japan during July-August 2023, with a focus on 2 key age groups, 0-15 and >80 years. We estimated overall seroprevalence of 45.3% for nucleocapsid antibodies and 95.4% for spike antibodies and found notable maternally derived spike antibodies in infants 6-11 months of age (90.0%).


Subject(s)
Antibodies, Viral , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/immunology , Seroepidemiologic Studies , Japan/epidemiology , SARS-CoV-2/immunology , Infant , Child , Antibodies, Viral/blood , Antibodies, Viral/immunology , Child, Preschool , Adult , Adolescent , Young Adult , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Aged, 80 and over , Infant, Newborn , Female , Male , Aged , Middle Aged , Spike Glycoprotein, Coronavirus/immunology
12.
Cell Rep ; 43(5): 114235, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38748880

ABSTRACT

Nanoparticle vaccines displaying mosaic receptor-binding domains (RBDs) or spike (S) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other sarbecoviruses are used in preparedness against potential zoonotic outbreaks. Here, we describe a self-assembling nanoparticle using lumazine synthase (LuS) as the scaffold to display RBDs from different sarbecoviruses. Mosaic nanoparticles induce sarbecovirus cross-neutralizing antibodies comparable to a nanoparticle cocktail. We find mosaic nanoparticles elicit a B cell receptor repertoire using an immunodominant germline gene pair of IGHV14-3:IGKV14-111. Most of the tested IGHV14-3:IGKV14-111 monoclonal antibodies (mAbs) are broadly cross-reactive to clade 1a, 1b, and 3 sarbecoviruses. Using mAb competition and cryo-electron microscopy, we determine that a representative IGHV14-3:IGKV14-111 mAb, M2-7, binds to a conserved epitope on the RBD, largely overlapping with the pan-sarbecovirus mAb S2H97. This suggests mosaic nanoparticles expand B cell recognition of the common epitopes shared by different clades of sarbecoviruses. These results provide immunological insights into the cross-reactive responses elicited by mosaic nanoparticles against sarbecoviruses.


Subject(s)
Nanoparticles , Nanoparticles/chemistry , Animals , Humans , SARS-CoV-2/immunology , Antibodies, Viral/immunology , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Mice , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Cross Reactions/immunology , Antibody Formation/immunology , COVID-19/immunology , COVID-19/virology , Protein Domains , Mice, Inbred BALB C , Multienzyme Complexes/immunology , Female , Immunodominant Epitopes/immunology
13.
PLoS One ; 19(5): e0304477, 2024.
Article in English | MEDLINE | ID: mdl-38820301

ABSTRACT

BACKGROUND: Health personnel (HP) are on the frontlines during response to public health emergencies like COVID-19. This risk of exposure suggests the need for safety in responding to any pandemic. Therefore, to ascertain the rate of SARS-CoV-2 infection and immunity, and their determinants amongst HP become relevant. METHODS: A cross sectional health facility-based study was carried-out amongst HP in the Centre Region of Cameroon from 1st February to 30th June 2021. Characteristics and access to preventive tools were collected using face-to-face administered questionnaire. Nasopharyngeal swabs and whole blood were collected for PCR, IgG and IgM testing respectively. STATA version 17 software was used for data analysis. Determinants of COVID-19 infection were explored by estimating crude and adjusted Odd Ratio. RESULTS: Out of 510 HP reached, 458 were enrolled with mean age of 35 (±10) years. Thirty-four (7.4%) were PCR-positive to SARS-CoV-2 with 73.5% being clinicians versus 9 (26.4%) non-clinicians (p = 0.05). Sero-positivity to SARS-CoV-2 IgG/IgM was 40.2% (184/458), with 84.2% being clinicians versus 29 (15.8%) non-clinicians (p = 0.733). Amongst the 34 HP with PCR-positivity, 16 (47%) had no antibodies, while, 15 (44%) were IgG only. An estimate of HP (43.7%) had at least an evidence of PCR, IgG or IgM contact to COVID-19. Determinants of PCR-positivity was being clinical staff (AOR = 0.29, P = 0.039); and that of IgG/IgM were being non clinical staff (AOR = 0.41, p = 0.018) and regular use of face masks (AOR = 0.44, p = 0.001). HP trained on IPC (24%) were mainly from peripheral level (74.7%, p = 0.002). CONCLUSION: Active infections were within the range of pandemic control (<10%). However, around two-fifths of participants have had contact with the virus, indicating that HP remains a population at risk of COVID-19 and other similarly-transmitted epidemic prone diseases, and also an important source of transmission. There is need of vaccine to achieve protectiveness, and optimal response also requires capacity building to improve the health system when challenged by a future pandemic.


Subject(s)
Antibodies, Viral , COVID-19 , Health Personnel , Public Health , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , Cameroon/epidemiology , Male , Adult , Female , SARS-CoV-2/immunology , Cross-Sectional Studies , Antibodies, Viral/blood , Antibodies, Viral/immunology , Middle Aged , Disease Outbreaks , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood
14.
PLoS One ; 19(5): e0304534, 2024.
Article in English | MEDLINE | ID: mdl-38820303

ABSTRACT

Highly variable pandemic coronavirus SARS-CoV-2, which causes the hazardous COVID-19 infection, has been persistent in the human population since late 2019. A prompt assessment of individual and herd immunity against the infection can be accomplished by using rapid tests to determine antiviral antibody levels. The microneutralization assay (MN) is one of the most widely used diagnostic methods that has been proposed to assess the qualitative and quantitative characteristics of virus-specific humoral immunity in COVID-19 convalescents or vaccine recipients. However, some aspects of the assay, such as sensitivity and time cost, need improvement. Here, we developed an express test, which may be potentially used in clinical practice for the assessment of serum-caused SARS-CoV-2 inhibition in infected cell cultures. It implies the detection and counting of coronaviral fluorescent-forming units (FFU) and includes two sequentially used developing components: biotinylated mouse monoclonal antibodies against the recombinant N protein of SARS-CoV-2 (B.1) and the recombinant EGFP-streptavidin fusion protein. Due to the universal specificity of the antibodies, our analytical tool is suitable for the detection of various strains of SARS-CoV-2 when determining both the infectious titer of viruses and the titer of serum virus-neutralizing antibodies. The developed two-component test system is characterized by high sensitivity, a reduced number of analytic stages and low assay cost, as well as by flexibility, since it may be modified for detection of other pathogens using the appropriate antibodies.


Subject(s)
Antibodies, Viral , COVID-19 , SARS-CoV-2 , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Humans , COVID-19/diagnosis , COVID-19/virology , COVID-19/immunology , Animals , Antibodies, Viral/immunology , Antibodies, Viral/blood , Vero Cells , Chlorocebus aethiops , Mice , Fluorescent Antibody Technique/methods , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood
15.
Front Immunol ; 15: 1392477, 2024.
Article in English | MEDLINE | ID: mdl-38774878

ABSTRACT

Introduction: Accumulating evidence indicates the importance of T cell immunity in vaccination-induced protection against severe COVID-19 disease, especially against SARS-CoV-2 Variants-of-Concern (VOCs) that more readily escape from recognition by neutralizing antibodies. However, there is limited knowledge on the T cell responses across different age groups and the impact of CMV status after primary and booster vaccination with different vaccine combinations. Moreover, it remains unclear whether age has an effect on the ability of T cells to cross-react against VOCs. Methods: Therefore, we interrogated the Spike-specific T cell responses in healthy adults of the Dutch population across different ages, whom received different vaccine types for the primary series and/or booster vaccination, using IFNÉ£ ELISpot. Cells were stimulated with overlapping peptide pools of the ancestral Spike protein and different VOCs. Results: Robust Spike-specific T cell responses were detected in the vast majority of participants upon the primary vaccination series, regardless of the vaccine type (i.e. BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad26.COV2.S). Clearly, in the 70+ age group, responses were overall lower and showed more variation compared to younger age groups. Only in CMV-seropositive older adults (>70y) there was a significant inverse relation of age with T cell responses. Although T cell responses increased in all age groups after booster vaccination, Spike-specific T cell frequencies remained lower in the 70+ age group. Regardless of age or CMV status, primary mRNA-1273 vaccination followed by BNT162b2 booster vaccination showed limited booster effect compared to the BNT162b2/BNT162b2 or BNT162b2/mRNA-1273 primary-booster regimen. A modest reduction in cross-reactivity to the Alpha, Delta and Omicron BA.1, but not the Beta or Gamma variant, was observed after primary vaccination. Discussion: Together, this study shows that age, CMV status, but also the primary-booster vaccination regimen influence the height of the vaccination-induced Spike-specific T cell response, but did not impact the VOC cross-reactivity.


Subject(s)
COVID-19 , Cross Reactions , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , T-Lymphocytes , Humans , Cross Reactions/immunology , SARS-CoV-2/immunology , Middle Aged , Adult , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , Aged , Male , T-Lymphocytes/immunology , Female , Spike Glycoprotein, Coronavirus/immunology , Age Factors , Young Adult , COVID-19 Vaccines/immunology , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/prevention & control , Immunization, Secondary , Cytomegalovirus/immunology , BNT162 Vaccine/immunology , Vaccination , 2019-nCoV Vaccine mRNA-1273/immunology , ChAdOx1 nCoV-19/immunology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/immunology , Antibodies, Viral/blood , Aged, 80 and over
16.
Front Immunol ; 15: 1399180, 2024.
Article in English | MEDLINE | ID: mdl-38707896

ABSTRACT

Primary humoral deficiency and secondary B-cell depletion may lead to prolonged Sars-Cov-2 infection due to a decreased viral clearance. Prolonged infection is mainly driven by the lack of anti-Sars-Cov-2 immunoglobulin (IVIg) especially in patients with no vaccine response. Anti-spike immunoglobulin can be provided by infusion of convalescent patients' plasma: recent studies highlighted that commercial immunoglobulin show high titers of neutralizing IgG. We conducted a single center retrospective cohort. We included 9 patients (6 males, median age 74 years old): one patient with X-linked agammaglobulinemia and 8 patients treated with rituximab (2 granulomatosis with polyangiitis, 1 neuromyelitis optica, 4 low grade B-cell lymphoma and 1 EBV post-transplant lymphoproliferative disorder). Mean serum globulin was 4 ± 1.6 g/L. 7/8 had received at least 3 doses of mRNA anti-Sars-Cov-2 vaccine (median 4) with no response (anti-Spike IgG 0 for 6 patients). In this specific population requiring oxygen therapy but no intensive care support, the administration of IVIg was well tolerated and provided a swift improvement of clinical status, a significant decrease of inflammation associated to the an improvement of radiological patterns. Our results suggest that immunoglobulin could be used as a salvage therapy as an alternative to convalescent plasma but highly stringent patient selection is required due to the worldwide shortage of IVIg.


Subject(s)
COVID-19 , Immunocompromised Host , Immunoglobulins, Intravenous , SARS-CoV-2 , Humans , Male , Aged , Female , Immunoglobulins, Intravenous/therapeutic use , Immunoglobulins, Intravenous/administration & dosage , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/immunology , Retrospective Studies , Middle Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , Treatment Outcome , Immunization, Passive , COVID-19 Serotherapy , COVID-19 Drug Treatment
17.
PLoS One ; 19(5): e0304080, 2024.
Article in English | MEDLINE | ID: mdl-38768231

ABSTRACT

Human Papillomavirus (HPV) prophylactic vaccination has proven effective in preventing new infections, but it does not treat existing HPV infections or associated diseases. Hence, there is still an important reservoir of HPV in adults, as vaccination programs are mainly focused on young women. The primary objective of this non-randomized, open-label trial is to evaluate if a 3-dose regimen of Gardasil-9 in HPV16/18-positive women could reduce the infective capacity of their body fluids. We aim to assess if vaccine-induced antibodies could neutralize virions present in the mucosa, thus preventing the release of infective particles and HPV transmission to sexual partners. As our main endpoint, the E1^E4-HaCaT model will be used to assess the infectivity rate of cervical, anal and oral samples, obtained from women before and after vaccination. HPV DNA positivity, virion production, seroconversion, and the presence of antibodies in the exudates, will be evaluated to attribute infectivity reduction to vaccination. Our study will recruit two different cohorts (RIFT-HPV1 and RIFT-HPV2) of non-vaccinated adult women. RIFT-HPV1 will include subjects with an HPV16/18 positive cervical test and no apparent cervical lesions or cervical lesions eligible for conservative treatment. RIFT-HPV2 will include subjects with an HPV16/18 positive anal test and no apparent anal lesions or anal lesions eligible for conservative treatment, as well as women with an HPV16/18 positive cervical test and HPV-associated vulvar lesions. Subjects complying with inclusion criteria for both cohorts will be recruited to the main cohort, RIFT-HPV1. Three doses of Gardasil-9 will be administered intramuscularly at visit 1 (0 months), visit 2 (2 months) and visit 3 (6 months). Even though prophylactic HPV vaccines would not eliminate a pre-existing infection, our results will determine if HPV vaccination could be considered as a new complementary strategy to prevent HPV-associated diseases by reducing viral spread. Trial registration: https://clinicaltrials.gov/ct2/show/NCT05334706.


Subject(s)
Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 , Human papillomavirus 16 , Human papillomavirus 18 , Papillomavirus Infections , Humans , Female , Papillomavirus Infections/prevention & control , Papillomavirus Infections/virology , Papillomavirus Infections/immunology , Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/administration & dosage , Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/immunology , Human papillomavirus 16/immunology , Human papillomavirus 18/immunology , Adult , Young Adult , Adolescent , Antibodies, Viral/immunology , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/immunology , DNA, Viral , Vaccination/methods , Cervix Uteri/virology
18.
BMC Vet Res ; 20(1): 191, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734611

ABSTRACT

BACKGROUND: Many proteins of African swine fever virus (ASFV, such as p72, p54, p30, CD2v, K205R) have been successfully expressed and characterized. However, there are few reports on the DP96R protein of ASFV, which is the virulence protein of ASFV and plays an important role in the process of host infection and invasion of ASFV. RESULTS: Firstly, the prokaryotic expression vector of DP96R gene was constructed, the prokaryotic system was used to induce the expression of DP96R protein, and monoclonal antibody was prepared by immunizing mice. Four monoclonal cells of DP96R protein were obtained by three ELISA screening and two sub-cloning; the titer of ascites antibody was up to 1:500,000, and the monoclonal antibody could specifically recognize DP96R protein. Finally, the subtypes of the four strains of monoclonal antibodies were identified and the minimum epitopes recognized by them were determined. CONCLUSION: Monoclonal antibody against ASFV DP96R protein was successfully prepared and identified, which lays a foundation for further exploration of the structure and function of DP96R protein and ASFV diagnostic technology.


Subject(s)
African Swine Fever Virus , Antibodies, Monoclonal , Epitopes , Mice, Inbred BALB C , Viral Proteins , African Swine Fever Virus/immunology , Antibodies, Monoclonal/immunology , Animals , Epitopes/immunology , Mice , Viral Proteins/immunology , Antibodies, Viral/immunology , Swine , African Swine Fever/immunology , African Swine Fever/virology , Female
19.
Sci Rep ; 14(1): 10813, 2024 05 11.
Article in English | MEDLINE | ID: mdl-38734805

ABSTRACT

To evaluate the development of neutralizing Anti-Spike Protein IgG (Anti-S-IgG) during twin pregnancies before conception vs. during pregnancy. In this prospective study, three blood samples were collected from pregnant women and subjected to anti-S-IgG immunodiagnostics. The patient's medical records, including vaccination and PCR test results, were collected from the hospital's electronic database. Age-matched non-pregnant women were used as a control group. We enrolled 83 women with twin pregnancies. 49 women were vaccinated before conception, 21 women were vaccinated during pregnancy, and 13 were not vaccinated. Of the 13 women who weren't vaccinated, three became positive during pregnancy, and all three were severely ill. By contrast, in women who were vaccinated during or before pregnancy, COVID-19 infection during pregnancy caused only mild symptoms. A ten-fold lower level of neutralizing Anti-S-IgG in the 3rd trimester was observed in healthy women who were vaccinated before conception and remained healthy until discharge from the hospital after delivery 1605 (IQR: 763-2410) compared to the healthy women who were vaccinated during pregnancy 152 AU/mL (IQR: 54-360). This difference was higher among women who were infected by COVID-19 (as verified by a positive PCR test). The third-trimester level of neutralizing Ant-S-IgG in the infected group was 4770 AU/mL (4760-6100) in infected women vaccinated before conception compared to those vaccinated during pregnancy who had 70 AU/mL (IQR: 20-170) (p < 0.001). In women vaccinated at 13-16 weeks gestation, neutralizing Anti-S-IgG at 20-22 weeks went up to 372 AU/mL (IQR: 120-1598) but rapidly dropped to 112 AU/mL (IQR: 54-357) at 28-30 weeks, (p < 0.001), a faster decline than in women vaccinated at a median 22 weeks before conception. Being infected by COVID-19 before conception was linked to having low Anti-S-IgG levels during pregnancy, whereas being infected by COVID-19 during pregnancy led to a very high response in the 3rd trimester. In twin pregnancies, significantly lower neutralizing Anti-S-IgG levels were observed in women vaccinated during pregnancy compared to those vaccinated before conception, whether infected or not infected by COVID-19. A full course of vaccination before conception is recommended.Trial registration. ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: October 4, 2021. https://clinicaltrials.gov/ ID: NCT04595214.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunoglobulin G , Pregnancy, Twin , SARS-CoV-2 , Vaccination , Humans , Female , Pregnancy , Pregnancy, Twin/immunology , Adult , COVID-19/prevention & control , COVID-19/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Prospective Studies , SARS-CoV-2/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Spike Glycoprotein, Coronavirus/immunology
20.
Nat Commun ; 15(1): 4224, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762522

ABSTRACT

Waning antibody responses after COVID-19 vaccination combined with the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness. As a countermeasure, bivalent mRNA-based booster vaccines encoding the ancestral spike protein in combination with that of Omicron BA.1 or BA.5 were introduced. Since then, different BA.2-descendent lineages have become dominant, such as XBB.1.5, JN.1, or EG.5.1. Here, we report post-hoc analyses of data from the SWITCH-ON study, assessing how different COVID-19 priming regimens affect the immunogenicity of bivalent booster vaccinations and breakthrough infections (NCT05471440). BA.1 and BA.5 bivalent vaccines boosted neutralizing antibodies and T-cells up to 3 months after boost; however, cross-neutralization of XBB.1.5 was poor. Interestingly, different combinations of prime-boost regimens induced divergent responses: participants primed with Ad26.COV2.S developed lower binding antibody levels after bivalent boost while neutralization and T-cell responses were similar to mRNA-based primed participants. In contrast, the breadth of neutralization was higher in mRNA-primed and bivalent BA.5 boosted participants. Combined, our data further support the current use of monovalent vaccines based on circulating strains when vaccinating risk groups, as recently recommended by the WHO. We emphasize the importance of the continuous assessment of immune responses targeting circulating variants to guide future COVID-19 vaccination policies.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunization, Secondary , Immunogenicity, Vaccine , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , SARS-CoV-2/immunology , SARS-CoV-2/genetics , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/immunology , Antibodies, Viral/blood , Female , Male , Adult , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , T-Lymphocytes/immunology , Vaccination
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