Incorporation of a Novel CD4+ Helper Epitope Identified from Aquifex aeolicus Enhances Humoral Responses Induced by DNA and Protein Vaccinations

Xu, Ziyang; Chokkalingam, Neethu; Tello‐Ruiz, Edgar; Walker, Susanne; Kulp, Daniel W.; Weiner, David B.

doi:10.1016/j.isci.2020.101399

Cited by 13 publications

(13 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite these challenges, DNA vaccination still remains as an important strategy for in vivo delivery of NLTs, considering the cost-effectiveness of DNA production, high thermal stability of DNA plasmids 66,67 , the ability of DNA to potentiate in vivo expression of conformationally complex immunogens driven from larger cassettes to induce unique and relevant immune phenotypes 31,68 . The present study opens the door for exciting new studies aiming to deliver complex NLTs, such as cocktails or germlinetargeting immunogens, to rapidly execute pre-clinical NLT studies and to translate NLT immunogens to the clinic.…”

Section: Discussionmentioning

confidence: 99%

Structural identification of neutralizing antibodies induced by nucleic acid encoded native-like trimer

Xu¹,

Walker²,

Wise³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Despite extensive efforts, an efficacious HIV vaccine remains elusive. HIV Envelope (Env) is the target of all known neutralizing antibodies. Stabilizing Env into native-like trimer (NLT) conformations is required for recombinant protein immunogens to induce autologous neutralizing antibodies(nAbs) against difficult to neutralize HIV strains (tier-2) in rabbits and non-human primates. However, mice are the most cost effective and widely used vaccine model and mouse immunizations with NLTs have generally failed to induce tier-2 nAbs. Here, we explored if DNA-encoded NLTs would fold properly in vivo and induce an informed humoral response. We observed DNA encoding a BG505 NLT induces autologous tier-2 nAbs in mice, identified murine monoclonal neutralizing antibodies, mapped the responses to a new murine neutralizing Env C3/V5 epitope and determined the structures of Env-nAbs complexes. Beyond potential functional immunity gains, DNA vaccines permit in vivo folding of structured antigens and provide significant cost and speed advantages for enabling rapid evaluation of new HIV vaccines.

show abstract

Section: Discussionmentioning

confidence: 99%

Structural identification of neutralizing antibodies induced by nucleic acid encoded native-like trimer

Xu¹,

Walker²,

Wise³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…To develop multivalent vaccines, we genetically fused RBDs to a set of four different self-assembling scaffold proteins (Manolova et al, 2008;Kelly et al, 2019;Xu et al, 2020c;Zhao et al, 2014) with a potent CD4-helper epitope (LS-3) to help enhance germinal-center responses (Xu et al, 2020a). Tandem repeats of RBD have been shown to improve neutralization titers by 10-to 100-fold (Dai et al, 2020); thus, we displayed dimers of RBDs on some of our self-assembling scaffolds as well.…”

Section: Dna-launched Nanovaccines Amplify and Accelerate Immune Responsesmentioning

confidence: 99%

Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection

Konrath

Liaw

et al. 2022

Cell Reports

Self Cite

View full text Add to dashboard Cite

SARS-CoV-2 vaccines may target epitopes which reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and in vitro screening, we have incorporated glycans into the Receptor-Binding Domain (RBD) and assessed antigenic profiles. We demonstrate that glycan-coated RBD immunogens elicit stronger neutralizing antibodies and have engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicits potent neutralizing antibodies in guinea pigs, hamsters and multiple mouse models, including human ACE2 and human antibody repertoire transgenics. RBD nanoparticles induce high levels of cross-neutralizing antibodies against variants-of-concern with durable titers beyond six months. Single, low dose immunization protects against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of potent and durable coronavirus vaccines.

show abstract

“…Alternatively, as different vaccine delivery vehicles elicit a differential phenotype of immunity, distinct platforms could be used as tools to better understand which components of the immune response are desirable for broad efficacy, and could help to identify new correlates of protection. Although beyond the scope of this review, diverse vaccine platforms including conserved peptides ( 90 ), bivalent peptide conjugate vaccines (i.e., NCT00851266), DNA ( 91 , 92 ), mRNA ( 70 , 93 ), nanoparticle ( 94 , 95 ), or virus-like-particle (VLP) ( 96 , 97 ) based vaccines are undergoing evaluation as universal influenza virus vaccines, which could also protect against emerging pandemic HPAIs. Many of these alternative platforms are attractive because they can facilitate the delivery of multiple conserved Ags/epitopes simultaneously, some have inherent immunostimulatory or innate “adjuvanting” qualities which could increase breadth, some platforms present Ag in novel conformations such as repetitive particulate formulations (i.e., nanoparticle or VLP), and others are amenable to rapid customization and pandemic responsive scale-up.…”

Section: Novel Vaccination Strategies To Increase Influenza Vaccine Bmentioning

confidence: 99%

Adenoviral Vectors as Vaccines for Emerging Avian Influenza Viruses

et al. 2021

View full text Add to dashboard Cite

It is evident that the emergence of infectious diseases, which have the potential for spillover from animal reservoirs, pose an ongoing threat to global health. Zoonotic transmission events have increased in frequency in recent decades due to changes in human behavior, including increased international travel, the wildlife trade, deforestation, and the intensification of farming practices to meet demand for meat consumption. Influenza A viruses (IAV) possess a number of features which make them a pandemic threat and a major concern for human health. Their segmented genome and error-prone process of replication can lead to the emergence of novel reassortant viruses, for which the human population are immunologically naïve. In addition, the ability for IAVs to infect aquatic birds and domestic animals, as well as humans, increases the likelihood for reassortment and the subsequent emergence of novel viruses. Sporadic spillover events in the past few decades have resulted in human infections with highly pathogenic avian influenza (HPAI) viruses, with high mortality. The application of conventional vaccine platforms used for the prevention of seasonal influenza viruses, such as inactivated influenza vaccines (IIVs) or live-attenuated influenza vaccines (LAIVs), in the development of vaccines for HPAI viruses is fraught with challenges. These issues are associated with manufacturing under enhanced biosafety containment, and difficulties in propagating HPAI viruses in embryonated eggs, due to their propensity for lethality in eggs. Overcoming manufacturing hurdles through the use of safer backbones, such as low pathogenicity avian influenza viruses (LPAI), can also be a challenge if incompatible with master strain viruses. Non-replicating adenoviral (Ad) vectors offer a number of advantages for the development of vaccines against HPAI viruses. Their genome is stable and permits the insertion of HPAI virus antigens (Ag), which are expressed in vivo following vaccination. Therefore, their manufacture does not require enhanced biosafety facilities or procedures and is egg-independent. Importantly, Ad vaccines have an exemplary safety and immunogenicity profile in numerous human clinical trials, and can be thermostabilized for stockpiling and pandemic preparedness. This review will discuss the status of Ad-based vaccines designed to protect against avian influenza viruses with pandemic potential.

show abstract

Incorporation of a Novel CD4+ Helper Epitope Identified from Aquifex aeolicus Enhances Humoral Responses Induced by DNA and Protein Vaccinations

Cited by 13 publications

References 52 publications

Structural identification of neutralizing antibodies induced by nucleic acid encoded native-like trimer

Structural identification of neutralizing antibodies induced by nucleic acid encoded native-like trimer

Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection

Adenoviral Vectors as Vaccines for Emerging Avian Influenza Viruses

Contact Info

Product

Resources

About