scholarly journals Reduced infectivity but increased immune escape of the new SARS-CoV-2 variant of concern Omicron

2021 ◽  
Author(s):  
Jie Hu ◽  
Pai Peng ◽  
Kang Wu ◽  
Quan-xin Long ◽  
Juan Chen ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Immune Escape ◽  
Geometric Mean ◽  
Pseudotyped Virus ◽  
Original Strain ◽  
New Wave ◽  
Protein Subunit ◽  
And Control ◽  
Entry Efficiency

A new detected SARS-CoV-2 variant Omicron (B.1.1.529) had reported from more than 80 countries. In the past few weeks, a new wave of infection driven by Omicron is in progress. Omicron Spike (S) protein pseudotyped virus was used to determine the effect of S mutations on its capacity of infectivity and immune evasion. Our results showed the lower entry efficiency and less cleavage ability of Omicron than D614G variant. Pseudotype-based neutralizing assay was performed to analyze neutralizing antibodies elicited by previously infection or the RBD-based protein subunit vaccine ZF2001 against the Omicron variant. Sera sampled at around one month after symptom onset from 12 convalescents who were previously infected by SARS-CoV-2 original strain shows a more than 20-fold decrease of neutralizing activity against Omicron variant, when compared to D614G variant. Among 12 individuals vaccinated by RBD subunit vaccine, 58.3% (7/12) sera sampled at 15-60 days after 3rd-dose vaccination did not neutralize Omicron. Geometric mean titers (GMTs, 50% inhibitory dose [ID50]) of these sera against Omicron were 9.4-fold lower than against D614G. These results suggested a higher risk of Omicron breakthrough infections and reduced efficiency of the protective immunity elicited by existing vaccines. There are important implications about the modification and optimization of the current epidemic prevention and control including vaccine strategies and therapeutic antibodies against Omicron variant.

scholarly journals A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates

2021 ◽  
Author(s):  
Neil C Dalvie ◽  
Lisa H Tostanoski ◽  
Sergio A Rodriguez-Aponte ◽  
Kawaljit Kaur ◽  
Sakshi Bajoria ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Cellular Response ◽  
Subunit Vaccine ◽  
Hepatitis B Surface Antigen ◽  
Low Cost ◽  
Humoral Response ◽  
High Volume ◽  
Developed Countries ◽  
Protein Subunit ◽  
Middle Income

Vaccines against SARS-CoV-2 have been distributed at massive scale in developed countries, and have been effective at preventing COVID-19. Access to vaccines is limited, however, in low- and middle-income countries (LMICs) due to insufficient supply, high costs, and cold storage requirements. New vaccines that can be produced in existing manufacturing facilities in LMICs, can be manufactured at low cost, and use widely available, proven, safe adjuvants like alum, would improve global immunity against SARS-CoV-2. One such protein subunit vaccine is produced by the Serum Institute of India Pvt. Ltd. and is currently in clinical testing. Two protein components, the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen virus-like particles (VLPs), are each produced in yeast, which would enable a low-cost, high-volume manufacturing process. Here, we describe the design and preclinical testing of the RBD-VLP vaccine in cynomolgus macaques. We observed titers of neutralizing antibodies (>104) above the range of protection for other licensed vaccines in non-human primates. Interestingly, addition of a second adjuvant (CpG1018) appeared to improve the cellular response while reducing the humoral response. We challenged animals with SARS-CoV-2, and observed a ~3.4 and ~2.9 log10 reduction in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, compared to sham controls. These results inform the design and formulation of current clinical COVID-19 vaccine candidates like the one described here, and future designs of RBD-based vaccines against variants of SARS-CoV-2 or other betacoronaviruses.

scholarly journals Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment immunogen

2020 ◽  
Author(s):  
Sameer Kumar Malladi ◽  
Randhir Singh ◽  
Suman Pandey ◽  
Savitha Gayathri ◽  
Kawkab Kanjo ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Viral Vectors ◽  
Mammalian Cell Culture ◽  
Geometric Mean ◽  
High Yield ◽  
Great Promise ◽  
Protein Subunit ◽  
Protein Fragment ◽  
Subunit Vaccines ◽  
Major Impediment

AbstractVirtually all SARS-CoV-2 vaccines currently in clinical testing are stored in a refrigerated or frozen state prior to use. This is a major impediment to deployment in resource-poor settings. Several use viral vectors or mRNA. In contrast to protein subunit vaccines, there is limited manufacturing expertise for these novel, nucleic acid based modalities, especially in the developing world. Neutralizing antibodies, the clearest known correlate of protection against SARS-CoV-2, are primarily directed against the Receptor Binding Domain (RBD) of the viral spike protein. We describe a monomeric, glycan engineered RBD protein fragment that is expressed at a purified yield of 214mg/L in unoptimized, mammalian cell culture and in contrast to a stabilized spike ectodomain, is tolerant of exposure to temperatures as high as 100°C when lyophilized, upto 70°C in solution and stable for over four weeks at 37°C. In prime:boost guinea pig immunizations, when formulated with the MF59 like adjuvant AddaVax™, the RBD derivative elicited neutralizing antibodies with an endpoint geometric mean titer of ~415 against replicative virus, comparing favourably with several vaccine formulations currently in the clinic. These features of high yield, extreme thermotolerance and satisfactory immunogenicity suggest that such RBD subunit vaccine formulations hold great promise to combat COVID-19.

scholarly journals Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment

2020 ◽  
pp. jbc.RA120.016284
Author(s):  
Sameer Kumar Malladi ◽  
Randhir Singh ◽  
Suman Pandey ◽  
Savitha Gayathri ◽  
Kawkab Kanjo ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Viral Vectors ◽  
Mammalian Cell Culture ◽  
Geometric Mean ◽  
High Yield ◽  
Great Promise ◽  
Protein Subunit ◽  
Protein Fragment ◽  
Subunit Vaccines ◽  
Major Impediment

Virtually all SARS-CoV-2 vaccines currently in clinical testing are stored in a refrigerated or frozen state prior to use. This is a major impediment to deployment in resource-poor settings. Furthermore, several of them use viral vectors or mRNA. In contrast to protein subunit vaccines, there is limited manufacturing expertise for these nucleic acid-based modalities, especially in the developing world. Neutralizing antibodies, the clearest known correlate of protection against SARS-CoV-2, are primarily directed against the Receptor Binding Domain (RBD) of the viral spike protein, suggesting that a suitable RBD construct might serve as a more accessible vaccine ingredient. We describe a monomeric, glycan engineered RBD protein fragment that is expressed at a purified yield of 214 mg/L in unoptimized, mammalian cell culture and, in contrast to a stabilized spike ectodomain, is tolerant of exposure to temperatures as high as 100 °C when lyophilized, up to 70 °C in solution and stable for over four weeks at 37 °C. In prime:boost guinea pig immunizations, when formulated with the MF59-like adjuvant AddaVax™, the RBD derivative elicited neutralizing antibodies with an endpoint geometric mean titer of ~415 against replicative virus, comparing favourably with several vaccine formulations currently in the clinic. These features of high yield, extreme thermotolerance and satisfactory immunogenicity suggest that such RBD subunit vaccine formulations hold great promise to combat COVID-19.

scholarly journals Homologous or Heterologous Booster of Inactivated Vaccine Reduces SARS-CoV-2 Omicron Variant Escape from Neutralizing Antibodies

2021 ◽  
Author(s):  
Xun Wang ◽  
Xiaoyu Zhao ◽  
Jieyu Song ◽  
Jing Wu ◽  
Yuqi Zhu ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Inactivated Vaccine ◽  
Protein Subunit ◽  
The Third ◽  
Vaccine Booster ◽  
Push Forward ◽  
Rapid Transmission

The massive and rapid transmission of SARS-CoV-2 has led to the emergence of several viral variants of concern (VOCs), with the most recent one, B.1.1.529 (Omicron), which accumulated a large number of spike mutations, raising the specter that this newly identified variant may escape from the currently available vaccines and therapeutic antibodies. Using VSV-based pseudovirus, we found that Omicron variant is markedly resistant to neutralization of sera form convalescents or individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV). However, a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) significantly increased neutralization titers to both WT and Omicron variant. Moreover, at day 14 post the third dose, neutralizing antibody titer reduction for Omicron was less than that for convalescents or individuals who had only two doses of the vaccine, indicating that a homologous or heterologous booster can reduce the Omicron escape from neutralizing. In addition, we tested a panel of 17 SARS-CoV-2 monoclonal antibodies (mAbs). Omicron resists 7 of 8 authorized/approved mAbs, as well as most of the other mAbs targeting distinct epitopes on RBD and NTD. Taken together, our results suggest the urgency to push forward the booster vaccination to combat the emerging SARS-CoV-2 variants.

scholarly journals Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD protein vaccine against COVID-19 in adults: pooled analysis of two randomized, double-blind, placebo-controlled, phase 1 and 2 trials

2020 ◽  
Author(s):  
Shilong Yang ◽  
Yan Li ◽  
Lianpan Dai ◽  
Jianfeng Wang ◽  
Peng He ◽  
...  
Keyword(s):  
Adverse Events ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Phase 1 ◽  
Phase 2 ◽  
Protein Subunit ◽  
Phase 1 Study ◽  
Serious Adverse Events ◽  
Phase 2 Study ◽  
To Receive

SummaryBackgroundA safe and effective coronavirus disease 2019 (COVID-19) vaccine is urgently needed to control the ongoing pandemic. Although progress has been made recently with several candidates reporting positive efficacy results, COVID-19 vaccines developed so far cannot meet the global vaccine demand. We developed a protein subunit vaccine against COVID-19, using dimeric form of receptor-binding domain (RBD) as the antigen. We aimed to assess the safety and immunogenicity of this vaccine in humans and determine the appropriate dose and schedule for an efficacy study.MethodsWe did two randomized, double-blind, placebo-controlled, phase 1 and 2 trials for an RBD-based protein subunit vaccine, ZF2001. In phase 1 study, 50 healthy adults aged 18-59 years were enrolled and randomly allocated to three groups to receive three doses of vaccine (25 μg or 50 μg RBD-dimer, with adjuvant) or placebo (adjuvant-only) intramuscularly, 30 days apart. In phase 2 study, 900 healthy adults aged 18-59 years were enrolled and randomly allocated to six groups to receive vaccine (25 μg or 50 μg RBD-dimer, with adjuvant) or placebo (adjuvant-only) intramuscularly, with the former 3 groups given two doses and the latter 3 groups given three doses, 30 days apart. For phase 1 trial, the primary outcome was safety, as measured by the occurrence of adverse events and serious adverse events. The secondary outcome was immunogenicity as measured by the seroconversion rate and magnitude of antigen-binding antibodies, neutralizing antibodies and T-cell cytokine production. For phase 2 trial, the primary outcome included both safety and immunogenicity. These trials are registered with ClinicaTrials.gov, NCT04445194 and NCT04466085.FindingsBetween June 22 and September 15, 2020, 50 participants were enrolled to the phase 1 study (mean age 32.6 years) and 900 participants were enrolled to phase 2 study (mean age 43.5 years), to receive vaccine or placebo with a two-dose or three-dose schedule. For both trials, local and systemic adverse reactions were absent or mild in most participants. There were no serious adverse events related to vaccine in either trial. After three doses, neutralizing antibodies were detected in all participants receiving either 25 μg or 50 μg dose of vaccine in phase 1 study, and in 97% (the 25 μg group) and 93% (the 50 μg group) of participants, respectively, in phase 2 study. The SARS-CoV-2-neutralizing geometric mean titres (GMTs) were 94.5 for the 25 μg group and 117.8 for the 50 μg group in phase 1, and 102.5 for the 25 μg group and 69.1 for the 50 μg group in phase 2, exceeding the level of a panel of COVID-19 convalescent samples (GMT, 51). Vaccine induced balanced TH1 and TH2 responses. The 50 μg group did not show enhanced immunogenicity compared with the 25 μg group.InterpretationThe protein subunit vaccine ZF2001 is well-tolerated and immunogenic. The safety and immunogenicity data from phase 1 and 2 trials for ZF2001 support the use of 25 μg vaccine dose with three-dose schedule to an ongoing phase 3 large-scale evaluation for safety and efficacy.FundingNational Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical.

scholarly journals NEW INACTIVATED VACCINE AGAINST ENZOOTIC ENCEPHALOMYELITIS OF SWINES

2013 ◽  
Vol 17 ◽  
pp. 170-184
Author(s):  
S. V. Derevianko ◽  
V. I. Soroka ◽  
T. O. Bowa
Keyword(s):  
Neutralizing Antibodies ◽  
Virulent Strain ◽  
Geometric Mean ◽  
Vaccine Dose ◽  
Maximum Level ◽  
Original Method ◽  
Inactivated Vaccine ◽  
Technical Requirements ◽  
High Level ◽  
And Control

A specific inactivated vaccine for prevention of enzootic encephalomyelitis (Teschen disease) of swines was created. The vaccine is produced on the basis of «Dniprovskiy-34» strain of Porcine teschovirus-1 isolated in the Ukraine and adjuvant of ASRIAP. During vaccines production the original method of teshoviruses inactivation was used. A single vaccine dose of 2 cubic cm promotes specific swines immunity to Teschen disease remaining for 11 months. Protective antibody levels were observed on the 7th day after vaccination. The maximum level of virus neutralizing antibodies in the blood of vaccinated animals on 60th day have reached 1:8192. Geometric mean titer of antibodies is 1:512, which protects the vaccinated piglets even at intracerebral introduction of 10 lethal doses of control epizootic highly virulent strain of Teschen disease of swines «Chernihivskiy-2372». A high level of innovative product design was confirmed by commission tests conducted in cooperation with State Scientific Control Institute of Biotechnology and Microorganism Strains and protected with three patents of Ukraine for inventions and useful models. A normative product documentation (Technical Requirements of Ukraine, instructions for production and control and product insert) was created. Performed feasibility study of the «Teshovak» vaccine allows recommending it into the production and introduction into the practices of veterinary medicine.

scholarly journals Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda

2021 ◽  
Author(s):  
M&oacutenica L. Acevedo ◽  
Luis Alonso-Palomares ◽  
Andr&eacutes Bustamante ◽  
Aldo Gaggero ◽  
Fabio Paredes ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Neutralization Assay ◽  
Spike Protein ◽  
Pseudotyped Virus ◽  
South American ◽  
Virus Neutralization Assay ◽  
Alpha Variant ◽  
Vaccination Campaigns ◽  
The Impact

Background: The newly described SARS-CoV-2 lineage C.37 was recently classified as a variant of interest by the WHO (Lambda variant) based on its high circulation rates in South American countries and the presence of critical mutations in the spike protein. The impact of such mutations in infectivity and immune escape from neutralizing antibodies are entirely unknown. Methods: We performed a pseudotyped virus neutralization assay and determined the impact of the Lambda variant on infectivity and immune escape using plasma samples from healthcare workers (HCW) from two centers in Santiago, Chile who received the two-doses scheme of the inactivated virus vaccine CoronaVac. Results: We observed an increased infectivity mediated by the Lambda spike protein that was even higher than that of the D614G (lineage B) or the Alpha and Gamma variants. Compared to the Wild type (lineage A), neutralization was decreased by 3.05-fold for the Lambda variant while it was 2.33-fold for the Gamma variant and 2.03-fold for the Alpha variant. Conclusions: Our results indicate that mutations present in the spike protein of the Lambda variant of interest confer increased infectivity and immune escape from neutralizing antibodies elicited by CoronaVac. These data reinforce the idea that massive vaccination campaigns in countries with high SARS-CoV-2 circulation must be accompanied by strict genomic surveillance allowing the identification of new isolates carrying spike mutations and immunology studies aimed to determine the impact of these mutations in immune escape and vaccines breakthrough.

scholarly journals A Novel E2 Glycoprotein Subunit Marker Vaccine Produced in Plant Is Able to Prevent Classical Swine Fever Virus Vertical Transmission after Double Vaccination

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 418
Author(s):  
Youngmin Park ◽  
Yeonsu Oh ◽  
Miaomiao Wang ◽  
Llilianne Ganges ◽  
José Alejandro Bohórquez ◽  
...  
Keyword(s):  
Vertical Transmission ◽  
Classical Swine Fever Virus ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Vaccine Dose ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Tissue Samples ◽  
Marker Vaccine ◽  
E2 Glycoprotein

The efficacy of a novel subunit vaccine candidate, based in the CSFV E2 glycoprotein produced in plants to prevent classical swine fever virus (CSFV) vertical transmission, was evaluated. A Nicotiana benthamiana tissue culture system was used to obtain a stable production of the E2-glycoprotein fused to the porcine Fc region of IgG. Ten pregnant sows were divided into three groups: Groups 1 and 2 (four sows each) were vaccinated with either 100 μg/dose or 300 μg/dose of the subunit vaccine at 64 days of pregnancy. Group 3 (two sows) was injected with PBS. Groups 1 and 2 were boosted with the same vaccine dose. At 10 days post second vaccination, the sows in Groups 2 and 3 were challenged with a highly virulent CSFV strain. The vaccinated sows remained clinically healthy and seroconverted rapidly, showing efficient neutralizing antibodies. The fetuses from vaccinated sows did not show gross lesions, and all analyzed tissue samples tested negative for CSFV replication. However, fetuses of non-vaccinated sows had high CSFV replication in tested tissue samples. The results suggested that in vaccinated sows, the plant produced E2 marker vaccine induced the protective immunogenicity at challenge, leading to protection from vertical transmission to fetuses.

scholarly journals Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351, and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1421
Author(s):  
Yong Yang ◽  
Jinkai Zang ◽  
Shiqi Xu ◽  
Xueyang Zhang ◽  
Sule Yuan ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Neutralizing Antibodies ◽  
Wild Type Strain ◽  
Immune Escape ◽  
High Titer ◽  
Prototype Strain ◽  
Vaccine Antigen ◽  
Broadly Neutralizing Antibodies ◽  
Continued Use ◽  
Further Development

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the currently approved SARS-CoV-2 vaccines use the prototype strain-derived spike (S) protein or its receptor-binding domain (RBD) as the vaccine antigen. The emergence of several novel SARS-CoV-2 variants has raised concerns about potential immune escape. In this study, we performed an immunogenicity comparison of prototype strain-derived RBD, S1, and S ectodomain trimer (S-trimer) antigens and evaluated their induction of neutralizing antibodies against three circulating SARS-CoV-2 variants, including B.1.1.7, B.1.351, and B.1.617.1. We found that, at the same antigen dose, the RBD and S-trimer vaccines were more potent than the S1 vaccine in eliciting long-lasting, high-titer broadly neutralizing antibodies in mice. The RBD immune sera remained highly effective against the B.1.1.7, B.1.351, and B.1.617.1 variants despite the corresponding neutralizing titers decreasing by 1.2-, 2.8-, and 3.5-fold relative to that against the wild-type strain. Significantly, the S-trimer immune sera exhibited comparable neutralization potency (less than twofold variation in neutralizing GMTs) towards the prototype strain and all three variants tested. These findings provide valuable information for further development of recombinant protein-based SARS-CoV-2 vaccines and support the continued use of currently approved SARS-CoV-2 vaccines in the regions/countries where variant viruses circulate.

Sign in / Sign up

Export Citation Format

Share Document