Daniel W. Kulp
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Machine learning enables de novo multiepitope design of <i>Plasmodium falciparum</i> circumsporozoite protein to target trimeric L9 antibody Open
Currently approved vaccines for the prevention of malaria provide only partial protection against disease due to high variability in the quality of induced antibodies. These vaccines present the unstructured central repeat region, as well …
View article: Safety and pharmacokinetics of SARS-CoV-2 DNA-encoded monoclonal antibodies in healthy adults: a phase 1 trial
Safety and pharmacokinetics of SARS-CoV-2 DNA-encoded monoclonal antibodies in healthy adults: a phase 1 trial Open
Local intramuscular administration of synthetic plasmid DNA (pDNA) encoding monoclonal antibodies (mAb) offers an alternative to recombinant protein-based mAb delivery. In this phase 1 dose-escalation study, we evaluated the safety, tolera…
Rapid elicitation of a new class of neutralizing N332-glycan independent V3-glycan antibodies against HIV-1 in nonhuman primates Open
Sequential immunization is a promising approach to elicit broadly neutralizing antibodies (bNAbs) against the HIV-1 Envelope (Env). However, available protocols are inefficient and involve multiple immunizations over long periods of time. …
View article: Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies
Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies Open
Broadly neutralizing antibodies targeting the V2 apex of HIV-1 envelope are desired as vaccine design templates, but few have been described. Here, we report 11 lineages of V2 apex–neutralizing antibodies from simian-human immunodeficiency…
View article: Machine learning enables <i>de novo</i> multi-epitope design of plasmodium falciparum circumsporozoite protein to target trimeric L9 antibody
Machine learning enables <i>de novo</i> multi-epitope design of plasmodium falciparum circumsporozoite protein to target trimeric L9 antibody Open
Currently approved vaccines for the prevention of malaria provide only partial protection against disease, due to high variability in the quality of induced antibodies. These vaccines present the unstructured central repeat region, as well…
View article: Env-antibody coevolution identifies B cell priming as the principal bottleneck to HIV-1 V2 apex broadly neutralizing antibody development
Env-antibody coevolution identifies B cell priming as the principal bottleneck to HIV-1 V2 apex broadly neutralizing antibody development Open
Broadly neutralizing antibodies (bNAbs) are rarely elicited during HIV-1 infection. To identify obstacles to bNAb development, we longitudinally studied 122 rhesus macaques infected by one of 16 different simian-human immunodeficiency viru…
View article: Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV
Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV Open
Oncogenic forms of HPV account for 4.5% of the global cancer burden worldwide. This includes cervical, vaginal, vulvar, penile, and anal cancers, as well as head and neck cancers. As such, there is an urgent need to develop effective thera…
View article: Transient glycan-shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques
Transient glycan-shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques Open
SUMMARY Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 CD4-binding site (CD4bs) occur infrequently in macaques and humans and have not been reproducibly elicited in any outbred animal model. To address this challenge, we first…
View article: Deep Mining of the Human Antibody Repertoire Identifies Frequent and Genetically Diverse CDRH3 Topologies Targetable by Vaccination
Deep Mining of the Human Antibody Repertoire Identifies Frequent and Genetically Diverse CDRH3 Topologies Targetable by Vaccination Open
Germline targeting vaccination strategies against highly variable pathogens such as HIV aim to elicit broadly neutralizing antibodies (bnAbs) with particular immunogenetic or structural features. The V2 apex of the HIV Env protein is a pro…
View article: Growing Glycans in Rosetta: Accurate de novo glycan modeling, density fitting, and rational sequon design
Growing Glycans in Rosetta: Accurate de novo glycan modeling, density fitting, and rational sequon design Open
Carbohydrates and glycoproteins modulate key biological functions. However, experimental structure determination of sugar polymers is notoriously difficult. Computational approaches can aid in carbohydrate structure prediction, structure d…
View article: HIV-1 neutralizing antibodies in SHIV-infected macaques recapitulate structurally divergent modes of human V2 apex recognition with a single D gene
HIV-1 neutralizing antibodies in SHIV-infected macaques recapitulate structurally divergent modes of human V2 apex recognition with a single D gene Open
Broadly neutralizing antibodies targeting the V2 apex of the HIV-1 envelope trimer are among the most common specificities elicited in HIV-1-infected humans and simian-human immunodeficiency virus (SHIV)-infected macaques. To gain insight …
Format-tuning of in vivo-launched bispecific T cell engager enhances efficacy against renal cell carcinoma Open
Background Advanced clear cell renal cell carcinoma (ccRCC) is a prevalent kidney cancer for which long-term survival rates are abysmal, though immunotherapies are showing potential. Not yet clinically vetted are bispecific T cell engagers…
Involvement of ArlI, ArlJ, and CirA in archaeal type IV pilin-mediated motility regulation Open
Many prokaryotes use swimming motility to move toward favorable conditions and escape adverse surroundings. Regulatory mechanisms governing bacterial flagella-driven motility are well-established; however, little is yet known about the reg…
View article: Vaccination induces broadly neutralizing antibody precursors to HIV gp41
Vaccination induces broadly neutralizing antibody precursors to HIV gp41 Open
A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare …
View article: Heterologous prime-boost vaccination drives early maturation of HIV broadly neutralizing antibody precursors in humanized mice
Heterologous prime-boost vaccination drives early maturation of HIV broadly neutralizing antibody precursors in humanized mice Open
A protective HIV vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). Vaccination with the germline-targeting immunogen eOD-GT8 60mer adjuvanted with AS01 B was found to induce VRC01-class bnAb precursors in 97% of v…
Involvement of ArlI, ArlJ, and CirA in Archaeal Type-IV Pilin-Mediated Motility Regulation Open
Many prokaryotes use swimming motility to move toward favorable conditions and escape adverse surroundings. Regulatory mechanisms governing bacterial flagella-driven motility are well-established, however, little is yet known about the reg…
View article: Diverse competitor B cell responses to a germline-targeting priming immunogen in human Ig loci transgenic mice
Diverse competitor B cell responses to a germline-targeting priming immunogen in human Ig loci transgenic mice Open
Broadly neutralizing antibodies (bnAbs) have promise to protect against HIV infection, but induction of bnAbs by immunization is an unsolved vaccine design challenge. Germline-targeting priming immunogens aim to initiate the induction of b…
View article: In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates
In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates Open
COVID-19 remains a major public health concern. Monoclonal antibodies have received emergency use authorization (EUA) for pre-exposure prophylaxis against COVID-19 among high-risk groups for treatment of mild to moderate COVID-19. In addit…
Delineation of DNA and mRNA COVID-19 vaccine-induced immune responses in preclinical animal models Open
Nucleic acid vaccines are designed based on genetic sequences (DNA or mRNA) of a target antigen to be expressed in vivo to drive a host immune response. In response to the COVID-19 pandemic, mRNA and DNA vaccines based on the SARS-CoV-2 Sp…
Mucosal chemokine adjuvant supports heterologous protection against Delta and Omicron VOCs in the context of a SARS-CoV-2 wild-type DNA vaccine Open
Emerging variants of concern (VOCs) and waning vaccine-induced immunity challenge SARS-CoV-2 control. Directing vaccine-induced humoral and cell-mediated responses to mucosal surfaces could enhance vaccine efficacy and potentially reduce t…
Supplementary Data from A DNA-Launched Nanoparticle Vaccine Elicits CD8<sup>+</sup> T-cell Immunity to Promote <i>In Vivo</i> Tumor Control Open
Supplementary figures 1-4 and Supplementary Table 1
Supplementary Data from A DNA-Launched Nanoparticle Vaccine Elicits CD8<sup>+</sup> T-cell Immunity to Promote <i>In Vivo</i> Tumor Control Open
Supplementary figures 1-4 and Supplementary Table 1
Data from A DNA-Launched Nanoparticle Vaccine Elicits CD8<sup>+</sup> T-cell Immunity to Promote <i>In Vivo</i> Tumor Control Open
Cytolytic T cells (CTL) play a pivotal role in surveillance against tumors. Induction of CTL responses by vaccination may be challenging, as it requires direct transduction of target cells or special adjuvants to promote cross-presentation…
Data from A DNA-Launched Nanoparticle Vaccine Elicits CD8<sup>+</sup> T-cell Immunity to Promote <i>In Vivo</i> Tumor Control Open
Cytolytic T cells (CTL) play a pivotal role in surveillance against tumors. Induction of CTL responses by vaccination may be challenging, as it requires direct transduction of target cells or special adjuvants to promote cross-presentation…
Engineered antibody cytokine chimera synergizes with DNA-launched nanoparticle vaccines to potentiate melanoma suppression in vivo Open
Cancer immunotherapy has demonstrated great promise with several checkpoint inhibitors being approved as the first-line therapy for some types of cancer, and new engineered cytokines such as Neo2/15 now being evaluated in many studies. In …
Gene‐encoded nanoparticle vaccine platforms for in vivo assembly of multimeric antigen to promote adaptive immunity Open
Nanoparticle vaccines are a diverse category of vaccines for the prophylaxis or treatment of various diseases. Several strategies have been employed for their optimization, especially to enhance vaccine immunogenicity and generate potent B…
Delineation of DNA and mRNA COVID-19 vaccine-induced immune responses in preclinical animal models Open
Nucleic acid vaccines are designed based on genetic sequences (DNA or mRNA) of a target antigen to be expressed in vivo to drive a host immune response. In response to the COVID-19 pandemic, mRNA and DNA vaccines based on the SARS-CoV-2 Sp…