Lars Hangartner
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View article: Molecular parameters governing antibody FcγR signaling and effector functions in the context of HIV envelope
Molecular parameters governing antibody FcγR signaling and effector functions in the context of HIV envelope Open
Antibody effector functions contribute to the immune response to pathogens and can influence the efficacy of antibodies as therapeutics. To date, however, there is limited information on the molecular parameters that govern fragment crysta…
View article: The saponin monophosphoryl lipid A nanoparticle adjuvant induces dose-dependent HIV vaccine responses in nonhuman primates
The saponin monophosphoryl lipid A nanoparticle adjuvant induces dose-dependent HIV vaccine responses in nonhuman primates Open
Induction of durable protective immune responses is the main goal of prophylactic vaccines, and adjuvants play a role as drivers of such responses. Despite advances in vaccine strategies, development of a safe and effective HIV vaccine rem…
View article: Modulation of antigen delivery and lymph node activation in nonhuman primates by saponin adjuvant saponin/monophosphoryl lipid A nanoparticle
Modulation of antigen delivery and lymph node activation in nonhuman primates by saponin adjuvant saponin/monophosphoryl lipid A nanoparticle Open
Saponin-based vaccine adjuvants are potent in preclinical animal models and humans, but their mechanisms of action remain poorly understood. Here, using a stabilized HIV envelope trimer immunogen, we carried out studies in nonhuman primate…
View article: Modulation of antigen delivery and lymph node activation in non-human primates by saponin adjuvant SMNP
Modulation of antigen delivery and lymph node activation in non-human primates by saponin adjuvant SMNP Open
SUMMARY Saponin-based vaccine adjuvants are potent in preclinical animal models and humans, but their mechanisms of action remain poorly understood. Here, using a stabilized HIV envelope trimer immunogen, we carried out studies in non-huma…
View article: Dose-dependent regulation of immune memory responses against HIV by saponin monophosphoryl lipid A nanoparticle adjuvant
Dose-dependent regulation of immune memory responses against HIV by saponin monophosphoryl lipid A nanoparticle adjuvant Open
The induction of durable protective immune responses is the main goal of prophylactic vaccines, and adjuvants play an important role as drivers of such responses. Despite advances in vaccine strategies, a safe and effective HIV vaccine rem…
View article: Potent antibody-dependent cellular cytotoxicity of a V2-specific antibody is not sufficient for protection of macaques against SIV challenge
Potent antibody-dependent cellular cytotoxicity of a V2-specific antibody is not sufficient for protection of macaques against SIV challenge Open
Fc-mediated antibody effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can contribute to the containment HIV-1 replication but whether such activities are sufficient for protection is unclear. We previously ident…
View article: Potent antibody-dependent cellular cytotoxicity of a V2-specific antibody is not sufficient for protection of macaques against SIV challenge
Potent antibody-dependent cellular cytotoxicity of a V2-specific antibody is not sufficient for protection of macaques against SIV challenge Open
Fc-mediated antibody effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can contribute to the containment HIV-1 replication but whether such activities are sufficient for protection is unclear. We previously ident…
View article: Long-lasting germinal center responses to a priming immunization with continuous proliferation and somatic mutation
Long-lasting germinal center responses to a priming immunization with continuous proliferation and somatic mutation Open
Summary Germinal centers (GCs) are the engines of antibody evolution. Using HIV Env protein immunogen priming in rhesus monkeys (RM) followed by a long period without further immunization, we demonstrate GC B cells (B GC ) lasted at least …
View article: Internalization of HIV-1 by Phagocytes Is Increased When Virions Are Opsonized with Multimeric Antibody in the Presence of Complement
Internalization of HIV-1 by Phagocytes Is Increased When Virions Are Opsonized with Multimeric Antibody in the Presence of Complement Open
Antibody-mediated internalization of HIV-1 by phagocytes, a potential mechanism for clearing virus, is very inefficient. In an effort to improve viral clearance, we produced a multimeric form of the broadly neutralizing monoclonal antibody…
View article: Enhanced Ability of Plant-Derived PGT121 Glycovariants To Eliminate HIV-1-Infected Cells
Enhanced Ability of Plant-Derived PGT121 Glycovariants To Eliminate HIV-1-Infected Cells Open
PGT121 is a highly potent bNAb and its antiviral activities for HIV-1 prevention and therapy are currently being evaluated in clinical trials. The importance of its Fc-effector functions in clearing HIV-1-infected cells is also under inves…
View article: Effector function does not contribute to protection from virus challenge by a highly potent HIV broadly neutralizing antibody in nonhuman primates
Effector function does not contribute to protection from virus challenge by a highly potent HIV broadly neutralizing antibody in nonhuman primates Open
Effector function is not required for a potent HIV envelope–specific broadly neutralizing antibody to protect nonhuman primates from SHIV infection.
Accelerated Clearance and Degradation of Cell-Free HIV by Neutralizing Antibodies Occurs via FcγRIIb on Liver Sinusoidal Endothelial Cells by Endocytosis Open
Neutralizing Abs suppress HIV infection by accelerating viral clearance from blood circulation in addition to neutralization. The elimination mechanism is largely unknown. We determined that human liver sinusoidal endothelial cells (LSEC) …
Mapping Polyclonal Antibody Responses in Non-human Primates Vaccinated with HIV Env Trimer Subunit Vaccines Open
Rational immunogen design aims to focus antibody responses to vulnerable sites on primary antigens. Given the size of these antigens, there is, however, potential for eliciting unwanted, off-target responses. Here, we use our electron micr…
Mapping polyclonal antibody responses in non-human primates vaccinated with HIV Env trimer subunit vaccines Open
SUMMARY Rational immunogen design aims to focus antibody responses to vulnerable sites on the primary antigens. Given the size of these antigens there is however potential for eliciting unwanted, off-target responses. Here, we used our ele…
Reprogramming the antigen specificity of B cells using genome-editing technologies Open
We have developed a method to introduce novel paratopes into the human antibody repertoire by modifying the immunoglobulin (Ig) genes of mature B cells directly using genome editing technologies. We used CRISPR-Cas9 in a homology directed …
View article: Vaccine-induced protection from homologous Tier 2 simian-human immunodeficiency virus challenge in nonhuman primates
Vaccine-induced protection from homologous Tier 2 simian-human immunodeficiency virus challenge in nonhuman primates Open
SUMMARY Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (Tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection follo…
Reprogramming the antigen specificity of B cells using genomeediting technologies Open
We have developed a method to introduce novel paratopes into the human antibody repertoire by modifying the immunoglobulin genes of mature B cells directly using genome editing technologies. We used CRISPR-Cas9 in a homology directed repai…
View article: Electron-Microscopy-Based Epitope Mapping Defines Specificities of Polyclonal Antibodies Elicited during HIV-1 BG505 Envelope Trimer Immunization
Electron-Microscopy-Based Epitope Mapping Defines Specificities of Polyclonal Antibodies Elicited during HIV-1 BG505 Envelope Trimer Immunization Open
Characterizing polyclonal antibody responses via currently available methods is inherently complex and difficult. Mapping epitopes in an immune response is typically incomplete, which creates a barrier to fully understanding the humoral re…
Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design Open
HIV employs multiple means to evade the humoral immune response, particularly the elicitation of and recognition by broadly neutralizing antibodies (bnAbs). Such antibodies can act antivirally against a wide spectrum of viruses by targetin…