Intradermal ChAdOx1 Vaccine Following Two CoronaVac Shots: A Case Report

Inactivated SARS-CoV-2 vaccines are used in many countries with uncertain immunogenicity. Intradermal ChAdOx1 has been proposed as a resource-efficient heterologous third booster shot. A 52-year-old healthy male healthcare professional had received two intramuscular CoronaVac shots on 21 April and 23 May 2021, and volunteered to take a 0.1 mL ChAdOx1 vaccine intradermally on 29 June 2021, with minimal local reactions. The declining IgG levels against spike protein from the two CoronaVac shots increased to higher than 10,000 AU/mL two weeks after the intradermal ChAdOx1. Moreover, the neutralizing antibody increased from 66.77% to almost 100%. A ratio of 6.6:9.7 of IgA:IgG was observed. The 50% pseudovirus neutralization titer (PVNT50) against lentiviral pseudovirus bearing a codon-optimized spike gene (wild type, alpha, beta, and delta) were 1812.42, 822.99, 1025.42, 1347.13, respectively. The SARS-CoV-2-specific T cells to spike protein–peptide pools (532–788 SFU/106 PBMCs) were detected. In conclusion, the antibody and cellular responses to the intradermal ChAdOx1, as a third booster dose in a healthy volunteer who received two intramuscular CoronaVac shots, revealed a dramatic increase in the total antibodies, including IgG, IgA, as well as T cell responses against spike protein. The immune response from intradermal ChAdOx1 should be further investigated in a larger population.

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Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

Science Advances ◽

10.1126/sciadv.abg7156 ◽

2021 ◽

Vol 7 (22) ◽

pp. eabg7156

Author(s):

So-Hee Hong ◽

Hanseul Oh ◽

Yong Wook Park ◽

Hye Won Kwak ◽

Eun Young Oh ◽

...

Keyword(s):

Nucleocapsid Protein ◽

Nonhuman Primates ◽

Vaccine Candidate ◽

Statistical Significance ◽

Neutralizing Antibody ◽

Spike Protein ◽

Vaccine Candidates ◽

Cell Responses ◽

Antibody Levels ◽

Further Development

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

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Neutralizing antibody-independent immunity to SARS-CoV-2 in hamsters and hACE-2 transgenic mice immunized with a RBD/Nucleocapsid fusion protein

10.1101/2021.09.16.460663 ◽

2021 ◽

Author(s):

Julia Castro ◽

Marcilio Fumagalli ◽

Natalia Hojo-Souza ◽

Patrick Azevedo ◽

Natalia Salazar ◽

...

Keyword(s):

T Cell ◽

Transgenic Mice ◽

Lung Inflammation ◽

Neutralizing Antibodies ◽

Chimeric Protein ◽

Neutralizing Antibody ◽

Receptor Binding Domain ◽

Wild Type ◽

N Protein ◽

Cell Responses

The nucleocapsid (N) and the receptor binding domain (RBD) of the Spike (S) proteins elicit robust antibody and T cell responses either in vaccinated or COVID-19 convalescent individuals. We generated a chimeric protein that comprises the sequences of RBD from S and N antigens (SpiN). SpiN was highly immunogenic and elicited a strong IFNγ response from T cells and high levels of antibodies to the inactivated virus, but no neutralizing antibodies. Importantly, hamsters and the human Angiotensin Convertase Enzyme-2-transgenic mice immunized with SpiN were highly resistant to challenge with the wild type SARS-CoV-2, as indicated by viral load, clinical outcome, lung inflammation and lethality. Thus, the N protein should be considered to induce T-cell-based immunity to improve SARS-CoV-2 vaccines, and eventually to circumvent the immune scape by variants.

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First-in-Human Trial of a SARS CoV 2 Recombinant Spike Protein Nanoparticle Vaccine

10.1101/2020.08.05.20168435 ◽

2020 ◽

Cited By ~ 8

Author(s):

Cheryl Keech ◽

Gary Albert ◽

Patricia Reed ◽

Susan Neal ◽

Joyce S. Plested ◽

...

Keyword(s):

T Cell ◽

Adverse Events ◽

Immune Responses ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Healthy Adults ◽

Spike Protein ◽

Wild Type Virus ◽

Cell Responses ◽

The Mean

Background NVX-CoV2373 is a recombinant nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins. We present the Day 35 primary analysis of our trial of NVX-CoV2373 with or without the saponin-based Matrix-M1 adjuvant in healthy adults. Methods This is a randomized, observer-blinded, placebo-controlled, phase 1 trial in 131 healthy adults. Trial vaccination comprised two intramuscular injections, 21 days apart. Primary outcomes were reactogenicity, safety labs, and immunoglobulin G (IgG) anti-spike protein response. Secondary outcomes included adverse events, wild-type virus neutralizing antibody, and T-cell responses. Results Participants received NVX-CoV2373 with or without Matrix-M1 (n=106) or placebo (n=25). There were no serious adverse events. Reactogenicity was mainly mild in severity and of short duration (mean ≥ 2 days), with second vaccinations inducing greater local and systemic reactogenicity. The adjuvant significantly enhanced immune responses and was antigen dose-sparing, and the two-dose 5μg NVX-CoV2373/Matrix-M1 vaccine induced mean anti-spike IgG and neutralizing antibody responses that exceeded the mean responses in convalescent sera from COVID-19 patients with clinically significant illnesses. The vaccine also induced antigen-specific T cells with a largely T helper 1 (Th1) phenotype. Conclusions NVX-CoV2373/Matrix-M1 was well tolerated and elicited robust immune responses (IgG and neutralization) four-fold higher than the mean observed in COVID-19 convalescent serum from participants with clinical symptoms requiring medical care and induced CD4+ T-cell responses biased toward a Th1 phenotype. These findings suggest that the vaccine may confer protection and support transition to efficacy evaluations to test this hypothesis. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04368988).

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THE OMICRON VARIANT BREAKS THE EVOLUTIONARY LINEAGE OF SARS-COV2 VARIANTS

International Journal of Research -GRANTHAALAYAH ◽

10.29121/granthaalayah.v9.i12.2021.4418 ◽

2021 ◽

Vol 9 (12) ◽

pp. 108-132

Author(s):

Jean Claude Perez ◽

Valère Lounnas ◽

Montagnier Montagnier

Keyword(s):

Common Knowledge ◽

Helper Virus ◽

Spike Protein ◽

Gamma Delta ◽

Spike Gene ◽

New Variant ◽

The Usa ◽

Rna Fragments ◽

Alpha Beta ◽

Hairpin Conformation

We analyze here 7 very first strains of OMICRON the SARS-CoV2 new variant from South Africa, the USA (California and Minesota), Canada and Belgium. We applied, at the scale of the whole genome and the spike gene, the biomathematics method of Fibonacci meta-structure fractal analysis applied to the UA / CG proportions. We have evidenced the RUPTURE of OMICRON with respect to ALL the previous variants: D614G, ALPHA, BETA, GAMMA, DELTA. Remarkably, it is observed that the density of OMICRON mutations in the SPIKE PRION region is more than 8 times that of the rest of the Spike protein. In particular, we suggest that the mRNA stabilizing secondary structure ("hairpin" conformation) in the spike of all variants is degraded in OMICRON, probably making its mRNA more fragile. The loss of long-range fractal meta-structures in the OMICRON spike gene are in line with common knowledge on the mechanisms of epidemic ending, involving recombination of heavily mutated RNA fragments of the virus, with the possible inference of a distinct helper virus. This would indicate that the SARS-CoV2 is under very strong evolutionary pressure, possibly marking the end of the pandemic. We are studying more particularly the prion-like region of the spike, the mutations rate of which is 8 times higher in OMICRON than that of the whole spike protein.

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Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study

Nature Cancer ◽

10.1038/s43018-021-00274-w ◽

2021 ◽

Author(s):

Annika Fendler ◽

Scott T. C. Shepherd ◽

Lewis Au ◽

Katalin A. Wilkinson ◽

Mary Wu ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Hematological Malignancies ◽

Neutralizing Antibody ◽

Immune Monitoring ◽

Wild Type ◽

Patients With Cancer ◽

Cell Responses ◽

Solid Malignancies ◽

Cancer Types ◽

Anti Cd20

AbstractCoronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic.

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Local emergence and decline of a SARS-CoV-2 variant with mutations L452R and N501Y in the spike protein

10.1101/2021.04.27.21254849 ◽

2021 ◽

Author(s):

Jan-Philipp Mallm ◽

Christian Bundschuh ◽

Heeyoung Kim ◽

Niklas Weidner ◽

Simon Steiger ◽

...

Keyword(s):

Amino Acid ◽

Severe Acute Respiratory Syndrome ◽

Type Strain ◽

Wild Type Strain ◽

Population Level ◽

Spike Protein ◽

Whole Genome ◽

Wild Type ◽

Spike Gene ◽

Mutational Pattern

SummaryVariants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are replacing the initial wild-type strain, jeopardizing current efforts to contain the pandemic. Amino acid exchanges in the spike protein are of particular concern as they can render the virus more transmissible or reduce vaccine efficacy. Here, we conducted whole genome sequencing of SARS-CoV-2 positive samples from the Rhine-Neckar district in Germany during January-March 2021. We detected a total of 166 samples positive for a variant with a distinct mutational pattern in the spike gene comprising L18F, L452R, N501Y, A653V, H655Y, D796Y and G1219V with a later gain of A222V. This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains. These observations strongly argue for continuous and comprehensive monitoring of SARS-CoV-2 evolution on a population level.

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Four SARS-CoV-2 vaccines induce quantitatively different antibody responses against SARS-CoV-2 variants

10.1101/2021.09.27.21264163 ◽

2021 ◽

Author(s):

Marit J. van Gils ◽

Ayesha H.A. Lavell ◽

Karlijn van der Straten ◽

Brent Appelman ◽

Ilja Bontjer ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Adenovirus Vector ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Wild Type ◽

Fold Reduction ◽

Antibody Titers ◽

Alpha Beta ◽

Vaccination Campaigns

Emerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. We performed a head-to-head comparison of the ability of sera from individuals vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S) to recognize and neutralize the four SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma and Delta). Four weeks after completing the vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of BNT162b2 and mRNA-1273 (median titers of 1891 and 3061, respectively), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (median titers of 241 and 119, respectively). VOCs neutralization was reduced in all vaccine groups, with the largest (5.8-fold) reduction in neutralization being observed against the Beta variant. Overall, the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after the final vaccination.

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Glycan-masking spike antigen in NTD and RBD elicits broadly neutralizing antibodies against SARS-CoV-2 variants

10.1101/2021.11.01.466834 ◽

2021 ◽

Author(s):

Wei-Shuo Lin ◽

I-Chen Chen ◽

Hui-Chen Chen ◽

Yi-Chien Lee ◽

Suh-Chin Wu

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Fold Increase ◽

Vaccine Antigen ◽

Broadly Neutralizing Antibodies ◽

Neutralization Titer ◽

Cell Responses ◽

Folded Structure ◽

Antibody Titers ◽

The Impact

Glycan-masking the vaccine antigen by mutating the undesired antigenic sites with an additional N-linked glycosylation motif can refocus B-cell responses to desired/undesired epitopes, without affecting the antigen overall-folded structure. This study examine the impact of glycan-masking mutants of the N-terminal domain (NTD) and receptor-binding domain (RBD) of SARS-CoV-2, and found that the antigenic design of the S protein increases the neutralizing antibody titers against the Wuhan-Hu-1 ancestral strain and the recently emerged SARS-CoV-2 variants Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). Our results demonstrated that the use of glycan-masking Ad-S-R158N-Y160T in the NTD elicited a 2.8-fold, 6.5-fold, and 4.6-fold increase in the IC-50 NT titer against the Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2) variants, respectively. Glycan-masking of Ad-S-D428N in the RBD resulted in a 3.0-fold and 2.0-fold increase in the IC50 neutralization titer against the Alpha (B.1.1.7) and Beta (B.1.351) variants, respectively. The use of glycan-masking in Ad-S-R158N-Y160T and Ad-S-D428N antigen design may help develop universal COVID-19 vaccines against current and future emerging SARS-CoV-2 variants.

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Characterization of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein

Nature Communications ◽

10.1038/s41467-021-23166-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Pui Wang ◽

Siu-Ying Lau ◽

Shaofeng Deng ◽

Pin Chen ◽

Bobo Wing-Yee Mok ◽

...

Keyword(s):

Neutralizing Antibody ◽

T Cell Response ◽

Spike Protein ◽

Wild Type Virus ◽

Wild Type ◽

Cleavage Motif ◽

Sterilizing Immunity

AbstractSARS-CoV-2 is of zoonotic origin and contains a PRRA polybasic cleavage motif which is considered critical for efficient infection and transmission in humans. We previously reported on a panel of attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction of the spike protein. Here, we characterize pathogenicity, immunogenicity, and protective ability of a further cell-adapted SARS-CoV-2 variant, Ca-DelMut, in in vitro and in vivo systems. Ca-DelMut replicates more efficiently than wild type or parental virus in Vero E6 cells, but causes no apparent disease in hamsters, despite replicating in respiratory tissues. Unlike wild type virus, Ca-DelMut causes no obvious pathological changes and does not induce elevation of proinflammatory cytokines, but still triggers a strong neutralizing antibody and T cell response in hamsters and mice. Ca-DelMut immunized hamsters challenged with wild type SARS-CoV-2 are fully protected, with little sign of virus replication in the upper or lower respiratory tract, demonstrating sterilizing immunity.

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Distinct neutralizing kinetics and magnitudes elicited by different SARS-CoV-2 variant spikes

10.1101/2021.09.02.458740 ◽

2021 ◽

Author(s):

Yang Liu ◽

Jianying Liu ◽

Jing Zou ◽

Ping Ren ◽

Scott C. Weaver ◽

...

Keyword(s):

Rapid Evolution ◽

Neutralizing Antibody ◽

Cross Protection ◽

Wild Type ◽

Post Immunization ◽

Vaccine Booster ◽

Antibody Titers ◽

Alpha Beta

AbstractThe rapid evolution of SARS-CoV-2 mandates a better understanding of cross-protection between variants after vaccination or infection, but studies directly evaluating such cross-protection are lacking. Here we report that immunization with different variant spikes elicits distinct neutralizing kinetics and magnitudes against other SARS-CoV-2 variants. After immunizing hamsters with wild-type or mutant SARS-CoV-2 bearing variant spikes from Alpha, Beta, Gamma, or Epsilon, the animals developed faster and greater neutralization activities against homologous SARS-CoV-2 variants than heterologous variants, including Delta. The rank of neutralizing titers against different heterologous variants varied, depending on the immunized variant spikes. The differences in neutralizing titers between homologous and heterologous variants were as large as 62-, 15-, and 9.7-fold at days 14, 28, and 45 post-immunization, respectively. Nevertheless, all immunized hamsters were protected from challenges with all SARS-CoV-2 variants, including those exhibiting the lowest neutralizing antibody titers. The results provide insights into the COVID-19 vaccine booster strategies.

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