scholarly journals Receptor-binding domain recombinant protein RBD219-N1C1 on alum-CpG induces broad protection against SARS-CoV-2 variants of concern

2021 ◽  
Author(s):  
Jeroen Pollet ◽  
Ulrich Strych ◽  
Wen-Hsiang Chen ◽  
Leroy Versteeg ◽  
Brian Keegan ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Neutralizing Antibody ◽  
Vaccine Formulation ◽  
Broadly Neutralizing Antibodies ◽  
Phase 3 ◽  
Advanced Phase ◽  
Antibody Titers ◽  
Cellular Immune

We conducted preclinical studies in mice using a yeast-produced SARS-CoV-2 RBD219-N1C1 subunit vaccine candidate formulated with aluminum hydroxide (alum) and CpG deoxynucleotides. This vaccine formulation is similar to one that entered advanced phase 3 clinical development in India. We compared the immune response of mice vaccinated with RBD219-N1C1/alum to mice vaccinated with RBD219-N1C1/alum+CpG. We also evaluated mice immunized with RBD219-N1C1/alum+CpG and boosted with RBD219-N1C1/alum. Mice were immunized twice intramuscularly at a 21-day interval. Compared to two doses of the RBD219-N1C1/alum formulation, the RBD219-N1C1/alum+CpG vaccine induced a stronger and more balanced Th1/Th2 cellular immune response, with high levels of neutralizing antibodies against the original Wuhan isolate of SARS-CoV-2 as well as the B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.1 (Kappa) variants. Notably, the sera from mice that received two 7 μg doses of RBD219-N1C1/alum+CpG showed more than 18 times higher neutralizing antibody titers against B.1.351, than the WHO International Standard for anti-SARS-CoV-2 immunoglobulin NIBSC 20/136. Interestingly, a booster dose did not require the addition of CpG to induce this effect. The data reported here reinforces that the RBD219-N1C1/alum+CpG vaccine formulation is suitable for inducing broadly neutralizing antibodies against SARS-CoV-2 including three variants of concern, B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.1 (Kappa).

scholarly journals Distinct cellular immune signatures in acute Zika virus infection are associated with high or low persisting neutralizing antibody titers

2021 ◽  
Author(s):  
Elizabeth E. McCarthy ◽  
Pamela M. Odorizzi ◽  
Emma Lutz ◽  
Carolyn P. Smullin ◽  
Iliana Tenvooren ◽  
...  
Keyword(s):  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Immune Cell ◽  
Acute Infection ◽  
Neutralizing Antibody ◽  
Natural Immunity ◽  
Zikv Infection ◽  
Antibody Titers ◽  
Cellular Immune

Although the formation of a durable neutralizing antibody response after an acute viral infection is a key component of protective immunity, little is known about why some individuals generate high versus low neutralizing antibody titers to infection or vaccination. Infection with Zika virus (ZIKV) during pregnancy can cause devastating fetal outcomes, and efforts to understand natural immunity to this infection are essential for optimizing vaccine design. In this study, we leveraged the high-dimensional single-cell profiling capacity of mass cytometry (CyTOF) to deeply characterize the cellular immune response to acute and convalescent ZIKV infection in a cohort of blood donors in Puerto Rico incidentally found to be viremic during the 2015-2016 epidemic in the Americas. During acute ZIKV infection, we identified widely coordinated responses across innate and adaptive immune cell lineages. High frequencies of multiple activated innate immune subsets, as well as activated follicular helper CD4+ T cells and proliferating CD27-IgD- B cells, during acute infection were associated with high titers of ZIKV neutralizing antibodies at 6 months post-infection. On the other hand, low titers of ZIKV neutralizing antibodies were associated with immune features that suggested a cytotoxic-skewed immune "set-point." Our study offers insight into the cellular coordination of immune responses and identifies candidate cellular biomarkers that may offer predictive value in vaccine efficacy trials for ZIKV and other acute viral infections aimed at inducing high titers of neutralizing antibodies.

scholarly journals Effect of a booster-dose of rabies vaccine on the duration of virus neutralizing antibody titers in bovines

1998 ◽  
Vol 31 (4) ◽  
pp. 367-371 ◽  
Author(s):  
Avelino Albas ◽  
Paulo Eduardo Pardo ◽  
Albério Antonio Barros Gomes ◽  
Fernanda Bernardi ◽  
Fumio Honma Ito
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Booster Dose ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Rabies Vaccine ◽  
Western Region ◽  
Humoral Immune ◽  
Paulo State ◽  
Antibody Titers

Humoral immune response using inactivated rabies vaccine was studied in 35 nelore cross-bred bovines of western region of São Paulo state. Ninety days after vaccination, 13 (92.8%) animals presented titers 30.5IU/ml, through mouse neutralization test. After 180 days, 9 (64.3%) sera showed titers 30.5IU/ml, after 270 days, only one (7.1%) showed a titer of 0.51IU/ml, and after 360 days, all animals showed titers < 0.5IU/ml. Group of animals receiving booster dose 30 days after vaccination presented, two months after, all with titers > 0.5IU/ml. At 180 days, 17 (80.9%) sera presented titers > 0.5IU/ml; at 270 days, 15 (71.4%), with titers 30.5IU/ml and at 360 days, 4 (19.0%), with titers 30.5IU/ml. Booster-dose ensured high levels of neutralizing antibodies for at least three months, and 240 days after revaccination, 71.4% of animals were found with titers 30.5IU/ml.

scholarly journals Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

2021 ◽  
Author(s):  
Margherita Rosati ◽  
Mahesh Agarwal ◽  
Xintao Hu ◽  
Santhi Devasundaram ◽  
Dimitris Stellas ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Anatomical Site ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Antibody Titers ◽  
Cellular Immune

The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The DNA-only vaccine regimens were compared to a regimen that included co-immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques.

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

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.

scholarly journals Characterization of the Humoral Immune Response Induced after Infection with Atypical Porcine Pestivirus (APPV)

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 880 ◽  
Author(s):  
Gökce Nur Cagatay ◽  
Denise Meyer ◽  
Michael Wendt ◽  
Paul Becher ◽  
Alexander Postel
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Humoral Immune ◽  
Neutralizing Capacity ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Congenital Tremor

Atypical porcine pestivirus (APPV) is a widely distributed pathogen causing congenital tremor (CT) in piglets. So far, no data are available regarding the humoral immune response against APPV. In this study, piglets and their sows from an affected herd were tested longitudinally for viral genome and antibodies. APPV genome was detected in the majority of the piglets (14/15) from CT affected litters. Transient infection of gilts was observed. Kinetics of Erns- and E2-specific antibodies and their neutralizing capacity were determined by recently (Erns) and newly (E2) developed antibody ELISAs and virus neutralization assays. Putative maternally derived antibodies (MDA) were detected in most piglets, but displayed only low to moderate neutralizing capacity (ND50 ≤ 112). Horizontal APPV transmission occurred when uninfected and infected piglets were mingled on the flat deck. Horizontally infected piglets were clinically inapparent and showed only transient viremia with subsequently consistently high E2 antibody levels. For piglets from CT affected litters, significantly lower neutralizing antibody titers were observed. Results indicate that E2 represents the main target of neutralizing antibodies. Characterization of the humoral immune response against APPV will help to provide valuable serological diagnosis, to understand the epidemiology of this novel pathogen, and to implement tailored prevention strategies.

scholarly journals Recombinant adenovirus expressing vesicular stomatitis virus G proteins induce both humoral and cell-mediated immune responses in mice and goats

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Xiaojuan Xue ◽  
Zhaorong Yu ◽  
Hongyan Jin ◽  
Lin Liang ◽  
Jiayang Li ◽  
...  
Keyword(s):  
Immune Responses ◽  
G Proteins ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Recombinant Adenovirus ◽  
Neutralizing Antibody ◽  
Negative Control ◽  
Antibody Titers ◽  
Vesicular Stomatitis ◽  
Cellular Immune

Abstract Background Vesicular stomatitis (VS) is an acute, highly contagious and economically important zoonotic disease caused by the vesicular stomatitis virus (VSV). There is a need for effective and safe stable recombinant vaccine for the control of the disease. The human type 5 replication-defective adenovirus expression vector is a good way to construct recombinant vaccines. Results Three recombinant adenoviruses (rAd) were successfully constructed that expressed the VSV Indiana serotype glycoprotein (VSV-IN-G), VSV New Jersey serotype glycoprotein (VSV-NJ-G), and the G fusion protein (both serotypes of G [VSV-IN-G-NJ-G]) with potentiality to induce protective immunity. G proteins were successfully expressed with good immunogenicity. The rAds could induce the production of VSV antibodies in mice, and VSV neutralizing antibodies in goats, respectively. The neutralizing antibody titers could reach 1:32 in mice and 1:64 in goats. The rAds induced strong lymphocyte proliferation in mice and goats, which was significantly higher compared to the negative control groups. Conclusions The three rAds constructed in the study expressed VSV-G proteins and induced both humoral and cellular immune responses in mice and goats. These results lay the foundation for further studies on the use of rAds in vaccines expressing VSV-G.

scholarly journals Differential serological and neutralizing antibody dynamics after an infection by a single SARS-CoV-2 strain

2020 ◽  
Author(s):  
Emmanuelle Billon-Denis ◽  
Audrey Ferrier-Rembert ◽  
Annabelle Garnier ◽  
Laurence Cheutin ◽  
Clarisse Vigne ◽  
...  
Keyword(s):  
Immune Response ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Clinical Severity ◽  
Individual Factors ◽  
Receptor Binding Domain ◽  
Antibody Titers ◽  
Antibody Dynamics

Abstract BackgroundWe report here the case of two coworkers infected by the same SARS-CoV-2 strain, presenting two different immunological outcomes. CaseOne patient presented a strong IgG anti-receptor-binding domain immune response correlated with a low and rapidly decreasing titer of neutralizing antibodies. The other patient had similar strong IgG anti-receptor-binding domain immune response but high neutralizing antibody titers. Discussion and ConclusionThus, host individual factors may be the main drivers of the immune response varying with age and clinical severity.

scholarly journals Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants

2021 ◽  
Vol 12 ◽  
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 epitopes, without affecting the antigen’s overall-folded structure. This study examined 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 IC-50 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.

Subunit influenza vaccine candidate based on CD154 fused to HAH5 increases the antibody titers and cellular immune response in chickens

2011 ◽  
Vol 152 (3-4) ◽  
pp. 328-337 ◽  
Author(s):  
Alaín González Pose ◽  
Julia Noda Gómez ◽  
Alina Venereo Sánchez ◽  
Armando Vega Redondo ◽  
Elsa Rodríguez Rodríguez ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Vaccine ◽  
Cellular Immune Response ◽  
Vaccine Candidate ◽  
Antibody Titers ◽  
Cellular Immune

scholarly journals Peptide enzyme‐linked immunosorbent assay (pELISA) as a possible alternative to the neutralization test for evaluating the immune response to IBV vaccine

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Qi Wu ◽  
Zhixian Lin ◽  
Jinsen Wu ◽  
Kun Qian ◽  
Hongxia Shao ◽  
...  
Keyword(s):  
Immune Response ◽  
Immunosorbent Assay ◽  
Neutralizing Antibodies ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Vital Role ◽  
Enzyme Linked Immunosorbent Assay ◽  
Infectious Bronchitis ◽  
Different Types ◽  
Antibody Titers

Abstract Background Infectious bronchitis virus (IBV), a coronavirus, is one of the most important poultry pathogens worldwide due to its multiple serotypes and poor cross-protection. Vaccination plays a vital role in controlling the disease. The efficacy of vaccination in chicken flocks can be evaluated by detecting neutralizing antibodies with the neutralization test. However there are no simple and rapid methods for detecting the neutralizing antibodies. Results In this study, a peptide enzyme-linked immunosorbent assay (pELISA) as a possible alternative to the neutralization test for evaluating the immune response to IBV vaccine was developed. The pELISA could indirect evaluate neutralizing antibody titers against different types of IBV in all tested sera. The titers measured with the pELISA had a coefficient of 0.83 for neutralizing antibody titers. Conclusions The pELISA could detect antibodies against different types of IBV in all tested sera. The pELISA has the potential to evaluate samples for IBV-specific neutralizing antibodies and surveillance the infection of IBV.

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