Correction: A Replicating Modified Vaccinia Tiantan Strain Expressing an Avian-Derived Influenza H5N1 Hemagglutinin Induce Broadly Neutralizing Antibodies and Cross-Clade Protective Immunity in Mice

ABSTRACT This report summarizes a consultation meeting convened by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), on 12 September 2017 to discuss the scientific rationale for selectively testing relevant HIV vaccine candidates in early life that are designed to initiate immune responses for lifelong protective immunity. The urgent need to develop interventions providing durable protective immunity to HIV before sexual debut coupled with the practicality of infant vaccine schedules supports optimizing infant HIV vaccines as a high priority. The panelists discussed the unique opportunities and challenges of testing candidate HIV vaccines in the context of distinct early-life immunity. Key developments providing rationale and grounds for cautious optimism regarding evaluation of early-life HIV vaccines include recent studies of early-life immune ontogeny, studies of HIV-infected infants demonstrating relatively rapid generation of broadly neutralizing antibodies (bNAbs), discovery of novel adjuvants active in early life, and cutting-edge sample-sparing systems biology and immunologic assays promising deep insight into vaccine action in infants. Multidisciplinary efforts toward the goal of an infant HIV vaccine are under way and should be nurtured and amplified. IMPORTANCE Young adults represent one of the highest-risk groups for new HIV infections and the only group in which morbidity continues to increase. Therefore, an HIV vaccine to prevent HIV acquisition in adolescence is a top priority. The introduction of any vaccine during adolescence is challenging. This meeting discussed the opportunities and challenges of testing HIV vaccine candidates in the context of the infant immune system given recent advances in our knowledge of immune ontogeny and adjuvant design and studies demonstrating that HIV-infected infants generate broadly neutralizing antibodies, a main target of HIV vaccines, more rapidly than adults. Considering the global success of pediatric vaccines, the concept of an HIV vaccine introduced in early life holds merit and warrants testing.

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Yeast-produced RBD-based recombinant protein vaccines elicit broadly neutralizing antibodies and durable protective immunity against SARS-CoV-2 infection

Cell Discovery ◽

10.1038/s41421-021-00315-9 ◽

2021 ◽

Vol 7 (1) ◽

Cited By ~ 1

Author(s):

Jinkai Zang ◽

Yuanfei Zhu ◽

Yu Zhou ◽

Chenjian Gu ◽

Yufang Yi ◽

...

Keyword(s):

Recombinant Protein ◽

Neutralizing Antibodies ◽

Protective Immunity ◽

Vaccine Dose ◽

Cost Effective ◽

Prototype Strain ◽

Broadly Neutralizing Antibodies ◽

Preclinical Development ◽

Virus Challenge ◽

Opening Up

AbstractMassive production of efficacious SARS-CoV-2 vaccines is essential for controlling the ongoing COVID-19 pandemic. We report here the preclinical development of yeast-produced receptor-binding domain (RBD)-based recombinant protein SARS-CoV-2 vaccines. We found that monomeric RBD of SARS-CoV-2 could be efficiently produced as a secreted protein from transformed Pichia pastoris (P. pastoris) yeast. Yeast-derived RBD-monomer possessed functional conformation and was able to elicit protective level of neutralizing antibodies in mice. We further designed and expressed a genetically linked dimeric RBD protein in yeast. The engineered dimeric RBD was more potent than the monomeric RBD in inducing long-lasting neutralizing antibodies. Mice immunized with either monomeric RBD or dimeric RBD were effectively protected from live SARS-CoV-2 virus challenge even at 18 weeks after the last vaccine dose. Importantly, we found that the antisera raised against the RBD of a single SARS-CoV-2 prototype strain could effectively neutralize the two predominant circulating variants B.1.1.7 and B.1.351, implying broad-spectrum protective potential of the RBD-based vaccines. Our data demonstrate that yeast-derived RBD-based recombinant SARS-CoV-2 vaccines are feasible and efficacious, opening up a new avenue for rapid and cost-effective production of SARS-CoV-2 vaccines to achieve global immunization.

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Broadly Neutralizing Antibodies (BNAbs): templates for HIV-1 vaccine design

Journal of Medical Discovery ◽

10.24262/jmd.2.4.17039 ◽

2017 ◽

Vol 2 (4) ◽

Cited By ~ 1

Author(s):

Lixin Yan ◽

◽

Lihong Liu ◽

Yilin Wang ◽

Xi Huang ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Vaccine Design ◽

Broadly Neutralizing Antibodies ◽

Hiv 1

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Faculty Opinions recommendation of Dose-response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725818229.793512456 ◽

2015 ◽

Author(s):

Cynthia Derdeyn ◽

S Abigail Smith

Keyword(s):

Dose Response ◽

Neutralizing Antibodies ◽

Response Curve ◽

Dose Response Curve ◽

Broadly Neutralizing Antibodies

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Faculty Opinions recommendation of Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726369545.793518839 ◽

2016 ◽

Author(s):

Stephen J Kent

Keyword(s):

Neutralizing Antibodies ◽

Broadly Neutralizing Antibodies ◽

Infected Cells ◽

Hiv 1

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Faculty Opinions recommendation of Elimination of HIV-1-infected cells by broadly neutralizing antibodies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726190699.793517949 ◽

2016 ◽

Author(s):

Boris Matija Peterlin

Keyword(s):

Neutralizing Antibodies ◽

Broadly Neutralizing Antibodies ◽

Infected Cells ◽

Hiv 1

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Unique structural solution from a VH3-30 antibody targeting the hemagglutinin stem of influenza A viruses

Nature Communications ◽

10.1038/s41467-020-20879-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Wayne D. Harshbarger ◽

Derrick Deming ◽

Gordon J. Lockbaum ◽

Nattapol Attatippaholkun ◽

Maliwan Kamkaew ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Influenza A ◽

Critical Role ◽

Binding Activity ◽

Human Antibody ◽

Broadly Neutralizing Antibodies ◽

Influenza A Viruses ◽

Universal Vaccine ◽

Structural Details ◽

Structural Solution

AbstractBroadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among VH3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of VH3-30 antibodies and reveals that 3I14 represents a novel structural solution within the VH3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV.

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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 ◽

10.3390/v13081421 ◽

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.

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A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies

Scientific Reports ◽

10.1038/s41598-021-84116-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jean-François Bruxelle ◽

Tess Kirilenko ◽

Nino Trattnig ◽

Yiqiu Yang ◽

Matteo Cattin ◽

...

Keyword(s):

Transgenic Mice ◽

Envelope Protein ◽

Protein Sequence ◽

Neutralizing Antibodies ◽

Human Antibody ◽

Broadly Neutralizing Antibodies ◽

Specific Antibodies ◽

Strong Binding ◽

Hiv Envelope ◽

Hiv 1

AbstractThe occurrence of oligomannose-specific broadly neutralizing antibodies (bnAbs) has spurred efforts to develop immunogens that can elicit similar antibodies. Here, we report on the antigenicity and immunogenicity of a CRM197-conjugate of a previously reported oligomannose mimetic. Oligomannose-specific bnAbs that are less dependent on interactions with the HIV envelope protein sequence showed strong binding to the glycoconjugates, with affinities approximating those reported for their cognate epitope. The glycoconjugate is also recognized by inferred germline precursors of oligomannose-specific bnAbs, albeit with the expected low avidity, supporting its potential as an immunogen. Immunization of human-antibody transgenic mice revealed that only a TLR4-stimulating adjuvant formulation resulted in antibodies able to bind a panel of recombinant HIV trimers. These antibodies bound at relatively modest levels, possibly explaining their inability to neutralize HIV infectivity. Nevertheless, these findings contribute further to understanding conditions for eliciting HIV-cross-reactive oligomannose-specific antibodies and inform on next steps for improving on the elicited response.

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