scholarly journals AIDS Vaccine Research Subcommittee (AVRS) Consultation: Early-Life Immunization Strategies against HIV Acquisition

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Anjali Singh ◽  
Sallie Permar ◽  
Tobias R. Kollmann ◽  
Ofer Levy ◽  
Mary Marovich ◽  
...  
Keyword(s):  
Early Life ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Sexual Debut ◽  
Risk Groups ◽  
Hiv Vaccine ◽  
Broadly Neutralizing Antibodies ◽  
Hiv Vaccines ◽  
Vaccine Candidates ◽  
Hiv Acquisition

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.

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.

scholarly journals Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Mackenzie M Shipley ◽  
Vidya Mangala Prasad ◽  
Laura E Doepker ◽  
Adam S Dingens ◽  
Duncan K Ralph ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Viral Escape ◽  
Single Infection ◽  
Structural Studies ◽  
Broadly Neutralizing Antibodies ◽  
Hiv Vaccines ◽  
Functional Development ◽  
Broadly Neutralizing Antibody

Stimulating broadly neutralizing antibodies (bnAbs) directly from germline remains a barrier for HIV vaccines. HIV superinfection elicits bnAbs more frequently than single infection, providing clues of how to elicit such responses. We used longitudinal antibody sequencing and structural studies to characterize bnAb development from a superinfection case. BnAb QA013.2 bound initial and superinfecting viral Env, despite its probable naïve progenitor only recognizing the superinfecting strain, suggesting both viruses influenced this lineage. A 4.15 Å cryo-EM structure of QA013.2 bound to native-like trimer showed recognition of V3 signatures (N301/N332 and GDIR). QA013.2 relies less on CDRH3 and more on framework and CDRH1 for affinity and breadth compared to other V3/glycan-specific bnAbs. Antigenic profiling revealed that viral escape was achieved by changes in the structurally-defined epitope and by mutations in V1. These results highlight shared and novel properties of QA013.2 relative to other V3/glycan-specific bnAbs in the setting of sequential, diverse antigens.

scholarly journals Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors

2018 ◽  
Vol 115 (29) ◽  
pp. 7569-7574 ◽  
Author(s):  
Fernando Aleman ◽  
Netanel Tzarum ◽  
Leopold Kong ◽  
Kenna Nagy ◽  
Jiang Zhu ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Structural Analysis ◽  
Neutralizing Antibodies ◽  
Antigenic Site ◽  
The Other ◽  
Maturation Process ◽  
Broadly Neutralizing Antibodies ◽  
Vaccine Candidates ◽  
Rational Vaccine Design ◽  
Hairpin Conformation

Elicitation of broadly neutralizing antibodies (bnAbs) is a leading strategy in rational vaccine design against antigenically diverse pathogens. Here, we studied a panel of monoclonal antibodies (mAbs) from mice immunized with the hepatitis C virus (HCV) envelope glycoproteins E1E2. Six of the mAbs recognize the conserved E2 antigenic site 412–423 (AS412) and cross-neutralize diverse HCV genotypes. Immunogenetic and structural analysis revealed that the antibodies originated from two different germline (GL) precursors and bind AS412 in a β-hairpin conformation. Intriguingly, the anti-HCV activity of one antibody lineage is associated with maturation of the light chain (LC), whereas the other lineage is dependent on heavy-chain (HC) maturation. Crystal structures of GL precursors of the LC-dependent lineage in complex with AS412 offer critical insights into the maturation process of bnAbs to HCV, providing a scientific foundation for utilizing the mouse model to study AS412-targeting vaccine candidates.

scholarly journals HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies

Immunity ◽  
2016 ◽  
Vol 45 (3) ◽  
pp. 483-496 ◽  
Author(s):  
Jon M. Steichen ◽  
Daniel W. Kulp ◽  
Talar Tokatlian ◽  
Amelia Escolano ◽  
Pia Dosenovic ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Design ◽  
Hiv Vaccine ◽  
Broadly Neutralizing Antibodies

scholarly journals Protective Immunity against SARS Subunit Vaccine Candidates Based on Spike Protein: Lessons for Coronavirus Vaccine Development

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Atin Khalaj-Hedayati
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Subunit Vaccine ◽  
Vaccine Development ◽  
Spike Protein ◽  
Effective Vaccine ◽  
Universal Vaccine ◽  
Health Security ◽  
Vaccine Candidates ◽  
Novel Coronavirus

The recent outbreak of the novel coronavirus disease, COVID-19, has highlighted the threat that highly pathogenic coronaviruses have on global health security and the imminent need to design an effective vaccine for prevention purposes. Although several attempts have been made to develop vaccines against human coronavirus infections since the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003, there is no available licensed vaccine yet. A better understanding of previous coronavirus vaccine studies may help to design a vaccine for the newly emerged virus, SARS-CoV-2, that may also cover other pathogenic coronaviruses as a potentially universal vaccine. In general, coronavirus spike protein is the major antigen for the vaccine design as it can induce neutralizing antibodies and protective immunity. By considering the high genetic similarity between SARS-CoV and SARS-CoV-2, here, protective immunity against SARS-CoV spike subunit vaccine candidates in animal models has been reviewed to gain advances that can facilitate coronavirus vaccine development in the near future.

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

2021 ◽  
Vol 7 (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.

scholarly journals Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates

2020 ◽  
Author(s):  
Christopher A. Cottrell ◽  
Jelle van Schooten ◽  
Charles A. Bowman ◽  
Meng Yuan ◽  
David Oyen ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Fusion Peptide ◽  
Antibody Responses ◽  
Envelope Glycoproteins ◽  
Broadly Neutralizing Antibodies ◽  
Vaccine Candidates ◽  
Hiv 1

AbstractThe induction of broad and potent immunity by vaccines is the key focus of research efforts aimed at protecting against HIV-1 infection. Soluble native-like HIV-1 envelope glycoproteins have shown promise as vaccine candidates as they can induce potent autologous neutralizing responses in rabbits and non-human primates. In this study, monoclonal antibodies were isolated and characterized from rhesus macaques immunized with the BG505 SOSIP.664 trimer to better understand vaccine-induced antibody responses. Our studies reveal a diverse landscape of antibodies recognizing immunodominant strain-specific epitopes and non-neutralizing neo-epitopes. Additionally, we isolated a subset of mAbs against an epitope cluster at the gp120-gp41 interface that recognize the highly conserved fusion peptide and the glycan at position 88 and have characteristics akin to several human-derived broadly neutralizing antibodies.

scholarly journals Functional development of a V3-specific broadly neutralizing antibody isolated from a case of HIV superinfection

2021 ◽  
Author(s):  
Mackenzie M. Shipley ◽  
Vidya Mangala Prasad ◽  
Laura E Doepker ◽  
Adam S Dingens ◽  
Duncan K Ralph ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Viral Escape ◽  
Single Infection ◽  
Structural Studies ◽  
Broadly Neutralizing Antibodies ◽  
Hiv Vaccines ◽  
Functional Development ◽  
Broadly Neutralizing Antibody

Stimulating broadly neutralizing antibodies (bnAbs) directly from germline remains a barrier for HIV vaccines. HIV superinfection elicits bnAbs more frequently than single infection, providing clues of how to elicit such responses. We used longitudinal antibody sequencing and structural studies to characterize bnAb development from a superinfection case. Mature bnAb QA013.2 bound both initial transmitted and superinfecting virus, but its inferred naïve bound only the superinfecting strain and was not neutralizing. QA013.2 requires residues spanning FWRH1-CDRH1 to attain breadth, which is uncommon for V3-specific bnAbs. A 4.15 Å cryo-EM structure of QA013.2 bound to heterologous native-like trimer showed recognition of V3 signatures (N301, N332, and GDIR). Antigenic profiling revealed that viral escape was achieved not only by changes in the structurally-defined epitope, but also by mutations in V1. These results highlight shared and distinct properties of QA013.2 relative to other V3-specific bnAbs in the setting of sequential, diverse antigenic variants.

scholarly journals Plant-made HIV vaccines and potential candidates

2020 ◽  
Author(s):  
Jocelyne Tremouillaux-Guiller ◽  
Khaled Moustafa ◽  
Kathleen Hefferon ◽  
Goabaone Gaobotse ◽  
Abdullah Makhzoum
Keyword(s):  
Neutralizing Antibodies ◽  
Opportunistic Infections ◽  
Broadly Neutralizing Antibodies ◽  
Hiv Vaccines ◽  
Therapeutic Vaccines ◽  
Hiv Therapy ◽  
The Past ◽  
Health Burdens ◽  
Anti Hiv ◽  
Hiv 1

Millions of people around the world suffer from heavy social and health burdens related to HIV/AIDS and its associated opportunistic infections. To reduce these burdens, preventive and therapeutic vaccines are required. Effective HIV vaccines have been under investigation for several decades using different animal models. Potential plant-made HIV vaccine candidates have also gained attention in the past few years. In addition to this, broadly neutralizing antibodies produced in plants which can target conserved viral epitopes and neutralize mutating HIV strains have been identified. Numerous epitopes of glycoproteins and capsid proteins of HIV-1 are a part of HIV therapy. Here, we discuss some recent findings aiming to produce anti-HIV-1 recombinant proteins in engineered plants for AIDS prophylactics and therapeutic treatments.

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