scholarly journals SARS-CoV-2 preS dTM vaccine booster candidates increase functional antibody responses and cross-neutralization against SARS-CoV-2 variants of concern in non-human primates

2021 ◽  
Author(s):  
Vincent Pavot ◽  
Catherine Berry ◽  
Michael Kishko ◽  
Natalie Anosova ◽  
Dean Huang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Protein Vaccine ◽  
Preclinical Models ◽  
Protein Subunit ◽  
Vaccine Candidates ◽  
Vaccine Booster ◽  
Cross Neutralization

Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that partly evade neutralizing antibodies has raised concerns of reduced vaccine effectiveness and increased infection. We previously demonstrated in preclinical models and in human clinical trials that our SARS-CoV-2 recombinant spike protein vaccine adjuvanted with AS03 (CoV2 preS dTM-AS03) elicits robust neutralizing antibody responses in naïve subjects. Here, the objective was to document the potency of various booster vaccine formulations in macaques previously vaccinated with mRNA or protein subunit vaccine candidates. We show that one booster dose of AS03-adjuvanted CoV2 preS dTM, D614 (parental) or B.1.351 (Beta), in monovalent or bivalent (D614 + B.1.351) formulations, significantly boosted pre-existing neutralizing antibodies and elicited high and stable cross-neutralizing antibodies covering the four known SARS-CoV-2 variants of concern (Alpha, Beta, Gamma and Delta) and, unexpectedly, SARS-CoV-1, in primed macaques. Interestingly, the non-adjuvanted CoV2 preS dTM B.1.351 vaccine formulation also significantly boosted and broadened the neutralizing antibody responses. Our findings show that these vaccine candidates used as a booster have the potential to offer cross-protection against a broad spectrum of variants. This has important implications for vaccine control of SARS-CoV-2 variants of concern and informs on the benefit of a booster with our vaccine candidates currently under evaluation in phase 2 and 3 clinical trials (NCT04762680 and NCT04904549).

scholarly journals SARS-CoV-2 preS dTM vaccine booster candidates increase functional antibody responses and cross-neutralization against SARS-CoV-2 variants of concern in non-human primates

2021 ◽  
Author(s):  
Vincent Pavot ◽  
Catherine Berry ◽  
Michael Kishko ◽  
Natalie G. Anosova ◽  
Dean Huang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Protein Vaccine ◽  
Protein Subunit ◽  
Vaccine Candidates ◽  
Link Type ◽  
Vaccine Booster ◽  
Cross Neutralization

AbstractThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that partly evade neutralizing antibodies has raised concerns of reduced vaccine effectiveness and increased infection. We previously demonstrated in preclinical models and in human clinical trials that our SARS-CoV-2 recombinant spike protein vaccine adjuvanted with AS03 (CoV2 preS dTM-AS03) elicits robust neutralizing antibody responses in naïve subjects. Here, the objective was to document the potency of various booster vaccine formulations in macaques previously vaccinated with mRNA or protein subunit vaccine candidates.We show that one booster dose of AS03-adjuvanted CoV2 preS dTM, D614 (parental) or B.1.351 (Beta), in monovalent or bivalent (D614 + B.1.351) formulations, significantly boosted pre-existing neutralizing antibodies and elicited high and stable cross-neutralizing antibodies covering the four known SARS-CoV-2 variants of concern (Alpha, Beta, Gamma and Delta) and, unexpectedly, SARS-CoV-1, in primed macaques. Interestingly, the non-adjuvanted CoV2 preS dTM B.1.351 vaccine formulation also significantly boosted and broadened the neutralizing antibody responses.Our findings show that these vaccine candidates used as a booster have the potential to offer cross-protection against a broad spectrum of variants. This has important implications for vaccine control of SARS-CoV-2 variants of concern and informs on the benefit of a booster with our vaccine candidates currently under evaluation in phase 2 and 3 clinical trials (NCT04762680 and NCT04904549).

scholarly journals A single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice

2020 ◽  
Author(s):  
Abigail E. Powell ◽  
Kaiming Zhang ◽  
Mrinmoy Sanyal ◽  
Shaogeng Tang ◽  
Payton A. Weidenbacher ◽  
...  
Keyword(s):  
Single Dose ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Amino Acid Deletion ◽  
Vaccine Candidates ◽  
Self Assembling ◽  
Antibody Titers

AbstractDevelopment of a safe and effective SARS-CoV-2 vaccine is a public health priority. We designed subunit vaccine candidates using self-assembling ferritin nanoparticles displaying one of two multimerized SARS-CoV-2 spikes: full-length ectodomain (S-Fer) or a C-terminal 70 amino-acid deletion (SΔC-Fer). Ferritin is an attractive nanoparticle platform for production of vaccines and ferritin-based vaccines have been investigated in humans in two separate clinical trials. We confirmed proper folding and antigenicity of spike on the surface of ferritin by cryo-EM and binding to conformation-specific monoclonal antibodies. After a single immunization of mice with either of the two spike ferritin particles, a lentiviral SARS-CoV-2 pseudovirus assay revealed mean neutralizing antibody titers at least 2-fold greater than those in convalescent plasma from COVID-19 patients. Additionally, a single dose of SΔC-Fer elicited significantly higher neutralizing responses as compared to immunization with the spike receptor binding domain (RBD) monomer or spike ectodomain trimer alone. After a second dose, mice immunized with SΔC-Fer exhibited higher neutralizing titers than all other groups. Taken together, these results demonstrate that multivalent presentation of SARS-CoV-2 spike on ferritin can notably enhance elicitation of neutralizing antibodies, thus constituting a viable strategy for single-dose vaccination against 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 Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2

2021 ◽  
Vol 14 (1) ◽  
pp. 39
Author(s):  
Iman Almansour ◽  
Nabela Calamata Macadato ◽  
Thamer Alshammari
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Serum Levels ◽  
Antibody Responses ◽  
Limited Data ◽  
Effective Measure ◽  
Vaccine Candidates ◽  
Cellular Immune

Since its identification in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has resulted in 46 million cases and more than one million deaths worldwide, as of 30 October 2020. Limited data exist on the magnitude and durability of antibodies generated by natural infection with SARS-CoV-2 and whether they can provide long-lasting immunity from reinfection. Vaccination has proven the most effective measure for controlling and preventing pandemics and, thus, development of a vaccine against COVID-19 is a top priority. However, the doses required to induce effective, long-lasting antibody responses against SARS-CoV-2 remain undetermined. Here, we present the development of SARS-CoV-2 vaccine candidates encoding the viral spike (S) gene, generated using plasmid (p)DNA technology, and we demonstrate the eliciting of S-specific antibodies in mice after three and four doses. The magnitude of binding and neutralizing antibody responses with three doses of synthetic, codon-optimized, full-length S (S.opt.FL) vaccine is comparable to that generated after four doses, suggesting that three doses are sufficient to elicit robust immune responses. Conversely, four doses of S1.opt pDNA vaccine, containing the S globular head, are required to elicit high levels of neutralizing antibodies. Furthermore, the S.opt.FL pDNA vaccine induces the highest serum levels of interferon (IFN)-γ, a marker for activation of cellular immune responses. Overall, our data show that three doses of S.FL pDNA vaccine elicit potent neutralizing antibody responses, with preclinical data that support the immunogenicity of these COVID-19 vaccine candidates and provide justification for further translational studies.

scholarly journals SARS-CoV-2 protein subunit vaccination elicits potent neutralizing antibody responses

2020 ◽  
Author(s):  
Marco Mandolesi ◽  
Daniel J Sheward ◽  
Leo Hanke ◽  
Junjie Ma ◽  
Pradeepa Pushparaj ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Host Cells ◽  
High Dose ◽  
Protein Subunit ◽  
High Dose Regimen ◽  
Antibody Titers ◽  
Protein Immunization

The outbreak and spread of SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), the cause of coronavirus disease 2019 (COVID-19), is a current global health emergency and a prophylactic vaccine is needed urgently. The spike glycoprotein of SARS-CoV-2 mediates entry into host cells, and thus is a target for neutralizing antibodies and vaccine design. Here we show that adjuvanted protein immunization with SARS-CoV-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques with neutralizing antibody titers orders of magnitude greater than those typically measured in serum from SARS-CoV-2 seropositive humans. Neutralizing antibody responses were observed after a single dose, with exceptionally high titers achieved after boosting. Furthermore, neutralizing antibody titers elicited by a dose-sparing regimen in mice were similar to those obtained from a high dose regimen. Taken together, these data strongly support the development of adjuvanted SARS-CoV-2 prefusion-stabilized spike protein subunit vaccines.

scholarly journals COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pinja Jalkanen ◽  
Pekka Kolehmainen ◽  
Hanni K. Häkkinen ◽  
Moona Huttunen ◽  
Paula A. Tähtinen ◽  
...  
Keyword(s):  
Health Care Workers ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Antibody Responses ◽  
Clinical Use ◽  
Infection Rates ◽  
Vaccine Candidates ◽  
Care Workers ◽  
Neutralization Titre ◽  
Cross Neutralization

AbstractAs SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees’ neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants.

scholarly journals Efficacy of an Adjuvanted Middle East Respiratory Syndrome Coronavirus Spike Protein Vaccine in Dromedary Camels and Alpacas

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 212 ◽  
Author(s):  
Danielle Adney ◽  
Lingshu Wang ◽  
Neeltje van Doremalen ◽  
Wei Shi ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Middle East ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
High Serum ◽  
Zoonotic Transmission ◽  
Spike Protein ◽  
Protein Vaccine ◽  
Protein Subunit ◽  
Dromedary Camels ◽  
Upper Airways

MERS-CoV is present in dromedary camels throughout the Middle East and Africa. Dromedary camels are the primary zoonotic reservoir for human infections. Interruption of the zoonotic transmission chain from camels to humans, therefore, may be an effective strategy to control the ongoing MERS-CoV outbreak. Here we show that vaccination with an adjuvanted MERS-CoV Spike protein subunit vaccine confers complete protection from MERS-CoV disease in alpaca and results in reduced and delayed viral shedding in the upper airways of dromedary camels. Protection in alpaca correlates with high serum neutralizing antibody titers. Lower titers of serum neutralizing antibodies correlate with delayed and significantly reduced shedding in the nasal turbinates of dromedary camels. Together, these data indicate that induction of robust neutralizing humoral immune responses by vaccination of naïve animals reduces shedding that potentially could diminish the risk of zoonotic transmission.

scholarly journals COVID-19 mRNA vaccine induced antibody responses and neutralizing antibodies against three SARS-CoV-2 variants

2021 ◽  
Author(s):  
Pinja Jalkanen ◽  
Pekka Kolehmainen ◽  
Hanni Häkkinen ◽  
Moona Huttunen ◽  
Paula Tähtinen ◽  
...  
Keyword(s):  
Health Care Workers ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Antibody Responses ◽  
Infection Rates ◽  
Vaccine Candidates ◽  
Care Workers ◽  
Neutralization Titre ◽  
The World ◽  
Cross Neutralization

Abstract As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees’ neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides strong evidence that the second dose of the BNT162b2 vaccine induces efficient cross-neutralization of SARS-CoV-2 variants currently circulating in the world.

scholarly journals Characterization of Neutralizing Antibody Responses Elicited by Clade A Envelope Immunogens Derived from Early Transmitted Viruses

2008 ◽  
Vol 82 (12) ◽  
pp. 5912-5921 ◽  
Author(s):  
Zane Kraft ◽  
Katharine Strouss ◽  
William F. Sutton ◽  
Brad Cleveland ◽  
For Yue Tso ◽  
...  
Keyword(s):  
Chronic Infection ◽  
Neutralizing Antibodies ◽  
Acute Infection ◽  
Variable Region ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Virus Envelope ◽  
Variable Regions ◽  
Clade B ◽  
Region Length

ABSTRACT The vast majority of studies with candidate immunogens based on the human immunodeficiency virus envelope (Env) have been conducted with Env proteins derived from clade B viruses isolated during chronic infection. Whether non-clade B Env protein immunogens will elicit antibodies with epitope specificities that are similar to those of antibodies elicited by clade B Envs and whether the antibodies elicited by Envs derived from early transmitted viruses will be similar to those elicited by Envs derived from viruses isolated during chronic infection are currently unknown. Here we performed immunizations with four clade A Envs, cloned directly from the peripheral blood of infected individuals during acute infection, which differed in lengths and extents of glycosylation. The antibody responses elicited by these four Envs were compared to each other and to those elicited by a well-characterized clade B Env immunogen derived from the SF162 virus, which was isolated during chronic infection. Only one clade A Env, the one with the fewer glycosylation sites, elicited homologous neutralizing antibodies (NAbs); these did not target the V1, V2, or V3 regions. In contrast, all four clade A Envs elicited anti-V3 NAbs against “easy-to-neutralize” clade B and clade A isolates, irrespective of the variable region length and extent of glycosylation of the Env used as an immunogen. These anti-V3 NAbs did not access their epitopes on homologous and heterologous clade A, or B, neutralization-resistant viruses. The length and extent of glycosylation of the variable regions on the clade A Env immunogens tested did not affect the breadth of the elicited NAbs. Our data also indicate that the development of cross-reactive NAbs against clade A viruses faces similar hurdles to the development of cross-reactive anti-clade B NAbs.

scholarly journals Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

2015 ◽  
Vol 23 (2) ◽  
pp. 84-94 ◽  
Author(s):  
David R. Martinez ◽  
Sallie R. Permar ◽  
Genevieve G. Fouda
Keyword(s):  
Immune Responses ◽  
Hiv Infection ◽  
Vaccine Efficacy ◽  
Neutralizing Antibody ◽  
Hiv Vaccine ◽  
Antibody Responses ◽  
Hiv Vaccines ◽  
Vaccine Candidates ◽  
Protective Antibodies ◽  
Pediatric Populations

ABSTRACTExtensive studies have demonstrated that infant immune responses are distinct from those of adults. Despite these differences, infant immunization can elicit protective immune responses at levels comparable to or, in some cases, higher than adult immune responses to many vaccines. To date, only a few HIV vaccine candidates have been tested in infant populations, and none of them evaluated vaccine efficacy. Recent exciting studies showing that HIV-infected infants can develop broad neutralizing antibody responses and that some HIV vaccine regimens can elicit high levels of potentially protective antibodies in infants provide support for the development and testing of HIV vaccines in pediatric populations. In this review, we discuss the differences in adult and infant immune responses in the setting of HIV infection and vaccination.

Sign in / Sign up

Export Citation Format

Share Document