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2022 ◽  
Vol 12 ◽  
Author(s):  
Wael Bahnan ◽  
Sebastian Wrighton ◽  
Martin Sundwall ◽  
Anna Bläckberg ◽  
Olivia Larsson ◽  
...  

Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.


2021 ◽  
Author(s):  
Tomabu Adjobimey ◽  
Julia Meyer ◽  
Leander Sollberg ◽  
Michael Bawolt ◽  
Christina Berens ◽  
...  

Abstract BACKGROUNDSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) have afflicted millions of people in a worldwide pandemic. Several vaccines have been developed to prevent infection and illness. However, the safety and efficacy of most of the vaccines currently available are still being questioned by part of the public opinion. Even if vaccine-resistant individuals represent a minority in most countries, their hesitancy is sufficient to delay the highly desired ‘herd-immunity threshold.’ METHODSIn an ongoing multinational trial, we collected blood samples from 365 adults, 18 years of age or older, vaccinated with mRNA vaccines (Moderna, BioNTech), viral DNA-vectored vaccines (AstraZeneca, Sputnik-V, and Johnson and Johnson), or the attenuated virus vaccine from Sinopharm. Out of the 365 vaccinated individuals included in the study, 41 received two doses of Moderna Biotech's Spikevax, 92 received two doses of BioNTech’s Comirnaty, 52 were vaccinated with two doses of Oxford-AstraZeneca’s Vaxzevria, 34 received one dose of Johnson and Johnson’s Jansen, 35 two doses of Gamaleja’s Sputnik-V and 28 two doses of Sinopharm’s BBIBP-CorV. In addition, 40 received a prime dose of AstraZeneca followed by BioNTech as a booster, whereas 43 received Moderna’s vaccine as a booster after a prime dose of AstraZeneca. After collecting reactogenicity data, the expression of S-Protein binding IgG and IgA were analyzed before and after full vaccination in each group using an automated sandwich ELISA system. In addition, the neutralizing capacity of sera from individuals from all groups was investigated using an ACE-2-RBD neutralizing assay. RESULTSThe main side effects reported included short-term mild-to-moderate pain at the injection site, fatigue, and headache. More severe side effects were reported by vaccinees in the Moderna (10%), AstraZeneca (11%), Johnson and Johnson (5.9%), and Sputnik-V (7.2%) groups. No severe adverse reaction was reported in the BioNTech group, and the Sinopharm vaccinees presented the mildest reactogenicity profile, with 93.8% of the vaccinees declaring no adverse reactions. Moderna’s vaccine induced the highest amounts of SARS-CoV-2 specific IgG, IgA, and serum neutralization activity compared to the other groups. In contrast, people vaccinated with Sinopharm and Johnson and Johnson’s vaccines have the lowest SARS-CoV-2-specific antibody titers. Vaccinees from the Johnson and Johnson group presented significant levels of SARS-CoV-2 specific IgA but not IgG compared to the controls before vaccination. In the Sinopharm group, neither IgG nor IgA expression was significant. In addition, sera from vaccinees of these two groups presented no significant neutralization potential compared to the unvaccinated controls. Significant negative correlations between age and SARS-CoV-2- specific IgG expression were observed in the Johnson and Johnson (r=-0.4414, p=0.009) and Sinopharm (r=-0.6108, p=0.0006) groups. Remarkably, younger vaccinees (18-60 years old) in both Sinopharm and Johnson and Johnson groups produced substantial SARS-CoV-2 specific antibody expression and exhibited significant neutralization potential. While the AstraZeneca vaccine alone induced moderate IgG and IgA expression, the combination with Moderna or BioNTech mRNA vaccines induced higher antibody levels than a double dose of AstraZeneca and similar IgG expression and neutralization potential compared to Moderna, or BioNTech used alone. CONCLUSIONThe results suggest that the Moderna vaccine is the most immunogenic after two doses. AstraZeneca and Sputnik-V presented moderate but significant antibody expression and virus neutralizing properties. Low antibody and neutralization potential was observed in the elderly vaccinated with Sinopharm or Johnson and Johnson vaccines. The data also suggest that heterologous vaccination strategies combining the AstraZeneca DNA vectored vaccines and mRNA vaccines Moderna or BioNTech booster induced more robust antibody and virus neutralization potential compared to their homologous counterparts.


2021 ◽  
Author(s):  
Wael Bahnan ◽  
Sebastian Wrighton ◽  
Martin Sundwall ◽  
Anna Bläckberg ◽  
Olivia Larsson ◽  
...  

Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization seems to affect the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.


2021 ◽  
Author(s):  
Shubham Shrivastava ◽  
Suhas T Mhaske ◽  
Meera S Modak ◽  
Rashmi G Virkar ◽  
Shamburaje S Pisal ◽  
...  

Abstract The emergence of novel variants of SARS-CoV-2 in several countries has been associated with the increased transmission/ reduced neutralization potential of antibodies against the Wuhan virus (wild type). Currently, India is recovering from an explosive second wave of COVID-19. This prospective study was conducted quarterly for one year (May 2020 to June 2021) at a tertiary care hospital, Pune city, western India. Receptor binding domain (RBD, n = 319) and full genome (n = 20) sequences from viral RNA positive nasopharyngeal swabs of COVID-19 patients representing first and second waves were used for analysis. We did not detect Brazil, South Africa and California variants. Till December, only wild type strain was prevalent. Concurrent with the upsurge of second wave in March-2021, 73% (33/45) of RBD sequences harboured L452R/E484Q mutations characteristic of Kappa variant. In April, co-circulation of Kappa (37%) and Delta (L452R/T478K, 59%) variants was recorded. During May and June, delta variant became the predominant circulating variant and coincided with a significant decline in the number of COVID-19 cases. Of the 20 full genome sequences, six isolates each exhibited signature mutations of Kappa and Delta variants respectively. With several states witnessing reduction in the number of COVID-19 cases, continuous monitoring of newer mutations and assessment of these mutations in influencing virus transmissibility and impact on vaccinated / previously exposed individuals would be necessary.


2021 ◽  
Vol 23 (09) ◽  
pp. 29-43
Author(s):  
Pooja S Dev ◽  
◽  
Dr. S. Meenatchisundaram ◽  

Objectives: The present study focuses on development of novel Metal-Herbal Nano composite (MHNC) formulation against Naja naja and Bungarus Caeruleus venoms on animal models. Methods: The venoms were procured from Irula snake catchers society in lyophilised forms. Herbal-metal nanocomposites were prepared in 1:1 combinations. Single strength concentration of Leucas zeylanica extracts and copper oxide metal nanoparticles was used to attain these ratio’s. In vivo venom neutralization analysis was carried out in Swiss albino mice. The LD50 and ED50 of the MHNC were determined. Results: The LD50 of the Naja naja venom was observed to be 0.19μg/g and 0.174μg/g for Bungarus Caeruleus venom. The ED50 of the MHNC against Naja naja venom was observed to be 14.22mg and 63.39mg for Bungarus Caeruleus venom. Conclusion: The MHNC developed in this study has significant venom neutralization potential against Naja naja and Bungarus Caeruleus venoms. Therefore, the MHNC can be used for development of anti-venom drugs.


Author(s):  
Padmanabha Shenoy ◽  
Sakir Ahmed ◽  
Aby Paul ◽  
Somy Cherian ◽  
Rashwith Umesh ◽  
...  

AbstractIntroductionSingle-dose COVID-19 vaccines in healthy individuals with past COVID-19 infections seem to provide better immunity than double doses in COVID-19 unexposed individuals. However, it is not known whether the same is true for patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressants.MethodsWe identified 30 patients with AIRD who took a single dose of the ChAdOx1 vaccine post-COVID-19 infection. Age, sex and disease similar patients were enrolled in to three groups of 30 each who had (1) past infection with COVID-19 but no vaccine, (2) a single dose of ChAdOx1 and (3) double doses of ChAdOx1. Sera were collected from each patient approximately 30 days after last vaccine dose or since the onset of COVID19 symptoms (in the unvaccinated group). Antibodies to spike protein were estimated and virus neutralization potential of sera was tested.ResultsBaseline characteristics including drug usage was similar betweenthe groups. Seroconversion occurred in 25(83%), 23(77%), 27(90%), and 30(100%) in natural infection, single-dose vaccine, double dose vaccine, and infection +single dose vaccine groups respectively. Mean antibody titres (10076.8±8998) in the last group were at least 6-100x higher than in the other 3 groups. Also, the infection +vaccine group had the highest neutralization potential of 83.37 % as compared to 45.4% in the fully vaccinated group.ConclusionThe hybrid immunity with a single dose of the vector-based vaccine post-infection seems to be superior to double dosage of the vaccine in patients with AIRD. A universal vaccination strategy involving a single dose of vaccine for all individuals with previous COVID-19 infection seems to be effective in these patients also.What is already known about this subject?A single dose of an RNA based COVID-19 vaccine after COVID-19 natural infection provides superior immune protection as compared to double doses of vaccines in infection naïve personsA second dose of vaccine in healthy people who had infection previously does not increase the immune protection but may paradoxically induce toleranceVaccine responses in patients with autoimmune rheumatic diseases(AIRD) may be suboptimal due to underlying disease or the use of immunosuppressants.What does this study add?Hybrid-induced immunity (single vaccine post COVID-19 infection) produces adequate vaccine responses in patients with AIRD, non-inferior to double dose of vaccineBesides mRNA vaccines, the adenoviral vector vaccine AZD1222 also demonstrates this hybrid phenomenon.How might this impact on clinical practice?Vaccination policies can consider providing only a single vaccine in those who had previous COVID-19 infection. This strategy has been shown not to be harmful for patients with AIRD. This will help reduce vaccine shortages.


2021 ◽  
Author(s):  
Denise Haslwanter ◽  
M. Eugenia Dieterle ◽  
Anna Z. Wec ◽  
Cecilia M. O'Brien ◽  
Mrunal Sakharkar ◽  
...  

Most known SARS-CoV-2 neutralizing antibodies (nAbs), including those approved by the FDA for emergency use, inhibit viral infection by targeting the receptor-binding domain (RBD) of the spike (S) protein. Variants of concern (VOC) carrying mutations in the RBD or other regions of S reduce the effectiveness of many nAbs and vaccines by evading neutralization. Therefore, therapies that are less susceptible to resistance are urgently needed. Here, we characterized the memory B-cell repertoire of COVID-19 convalescent donors and analyzed their RBD and non-RBD nAbs. We found that many of the non-RBD-targeting nAbs were specific to the N-terminal domain (NTD). Using neutralization assays with authentic SARS-CoV-2 and a recombinant vesicular stomatitis virus carrying SARS-CoV-2 S protein (rVSV-SARS2), we defined a panel of potent RBD and NTD nAbs. Next, we used a combination of neutralization-escape rVSV-SARS2 mutants and a yeast display library of RBD mutants to map their epitopes. The most potent RBD nAb competed with hACE2 binding and targeted an epitope that includes residue F490. The most potent NTD nAb epitope included Y145, K150 and W152. As seen with some of the natural VOC, the neutralization potencies of COVID-19 convalescent sera were reduced by 4-16-fold against rVSV-SARS2 bearing Y145D, K150E or W152R spike mutations. Moreover, we found that combining RBD and NTD nAbs modestly enhanced their neutralization potential. Notably, the same combination of RBD and NTD nAbs limited the development of neutralization-escape mutants in vitro, suggesting such a strategy may have higher efficacy and utility for mitigating the emergence of VOC.


2021 ◽  
Author(s):  
Pragya D Yadav ◽  
Gajanan Sapkal ◽  
Raches Ella ◽  
Rima R Sahay ◽  
Dimpal A Nyayanit ◽  
...  

Recently, multiple SARS-CoV-2 variants have been detected across the globe.The recent emergence of B.1.617 lineage has created serious public health problem in India. The high transmissibility was observed with this lineage which has led to daily increase in the number of SARS-CoV-2 infections. Apparently, the sub-lineage B.1.617.2 has slowly dominated the other variants including B1617.1, B.617.3 and B.1.1.7. With this, World Health Organization has described B.1.617.2 as variant of concern. Besides this, variant of concern B.1.351 has been also reported from India, known to showreducedefficacyfor many approved vaccines. With the increasing threat of the SARS-CoV-2 variants, it is imperative to assess the efficacy of the currently available vaccines against these variants. Here, we have evaluated the neutralization potential of sera collected from COVID-19 recovered cases (n=20) and vaccinees with two doses of BBV152 (n=17) against B.1.351 and B.1.617.2 compared to the prototype B.1 (D614G) variant.The finding of the study demonstrated a reduction in neutralization titers with sera of COVID-19 recovered cases(3.3-fold and 4.6-fold) and BBV152 vaccinees (3. 0 and 2.7 fold) against B.1.351 and B.1.617.2 respectively. Although, there is reduction in neutralization titer, the whole-virion inactivated SARS-CoV-2 vaccine (BBV152) demonstrates protective response against VOC B.1351 and B.1.617.2.


2021 ◽  
Author(s):  
Pragya Yadav ◽  
Gajanan N Sapkal ◽  
Priya Abraham ◽  
Gururaj Deshpande ◽  
Dimpal Nyayanit ◽  
...  

Covishield comprises the larger proportion in the vaccination program in India. Hence, it is of utmost importance to understand neutralizing capability of vaccine against the B.1.617.1 variant which is considered to responsible for surge of the cases in India. The neutralizing-antibody (NAb) titer against B.1.167.1 and prototype B.1 variant (D614G) was determined of the vaccine sera (4 weeks after second dose) of COVID-19 naive subjects (n=43) and COVID-19 recovered subjects (n=18). The results demonstrated that sera of COVID-19 recovered subjects (n=18) who received two doses of Covishield have higher NAb response compared to the COVID-19 naive with a significant difference (p<0.0001) in NAb titer against B.1 and B.1.617.1 In-spite of reduction in the neutralizing titer against B.1.617.1 variant; Covishield vaccine-induced antibodies are likely to be protective to limit the severity and mortality of the disease in the vaccinated individuals.


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