Biology subjects

Bouhuijs, J. H.

Publications and source records attributed to Bouhuijs, J. H..

4 recordsLinked to original sources

bioRxiv2026

Sequential vaccination matures VRC01-class HIV-1 neutralizing antibodies in humans

Inducing a broadly neutralizing antibody (bnAb) response is a key goal of HIV-1 vaccine development. Despite significant progress, it is unknown whether vaccine-primed B cells can be reactivated and matured to secrete bona fide bnAbs. In the IAVI C107/C110 single-arm, open-label human trial, VRC01-class memory B cells previously primed by the GT1.1 germline-targeting envelope glycoprotein (Env) trimer were reactivated by a BG505 SOSIP.664 trimer boost. Somatic hypermutation in the activated B cells drove higher antibody affinity for the CD4-binding site on fully glycosylated, heterologous Env trimers. Three VRC01-class monoclonal antibodies derived from independent B cell lineages neutralized 18-31% of 119 viruses in a globally diverse panel. This work advances the HIV-1 germline-targeting vaccination concept from proof-of-priming towards proof-of-breadth and defines a benchmark for bnAb induction.

immunology↗

bioRxiv2026

Adjuvant selection for optimally balanced humoral and cellular immunity induced by SARS-CoV-2 Spike virosome vaccines

Current SARS-CoV-2 vaccines provide limited breadth of protection, underscoring the need for vaccine strategies that optimize immune responses. Virosomesoffer a modular vaccine platform that enables multivalent antigen display and incorporation of adjuvants which can steer immune responses. We evaluated the immune response in BALB/c mice with virosomes displaying SARS-CoV-2 Wuhan or Delta spike antigens and coupled with various distinct adjuvants. Adjuvant selection differentially influenced both humoral and cellular immune outcomes. The TLR7/8 agonist 3M -052 induced a strong Th1-biased response, characterized by elevated IgG2a/IgG1 ratios and robust type 1 cytokine induction with suppression of Th2-associated cytokines. In contrast, the saponin QS-21 enhanced antibody functional quality, illustrated by improved virus neutralization potency and breadth. Furthermore, the combined incorporation of both 3M-052 and QS-21 induced an elevated Th1-biased response without improving neutralization capacity. In conclusion, different adjuvants added onto our virosome-basedvaccine led to distinct antibody responses and splenic T-cell profiles, reflective of differences in immune programming. This information guides the selection of adjuvants for respiratory virus vaccines.

immunology↗

bioRxiv2022

Bispecific antibodies combine breadth, potency, and avidity of parental antibodies to neutralize sarbecoviruses

SARS-CoV-2 mutational variants evade humoral immune responses elicited by vaccines and current monoclonal antibody (mAb) therapies. Novel antibody-based treatments will thus need to exhibit broad neutralization against different variants. Bispecific antibodies (bsAbs) combine the specificities of two distinct antibodies into one antibody taking advantage of the avidity, synergy and cooperativity provided by targeting two different epitopes. Here we used controlled Fab-arm exchange (cFAE), a versatile and straightforward method, to produce bsAbs that neutralize SARS-CoV and SARS-CoV-2 variants, including Omicron and its subvariants, by combining potent SARS-CoV-2-specific neutralizing antibodies with broader but less potent antibodies that also neutralize SARS-CoV. We demonstrate that the parental IgGs rely on avidity for their neutralizing activity by comparing their potency to bsAbs containing one irrelevant "dead" Fab arm. We used single particle mass photometry to measure formation of antibody:spike complexes, and determined that bsAbs increase binding stoichiometry compared to corresponding cocktails, without a loss of binding affinity. The heterogeneous binding pattern of bsAbs to spike (S), observed by negative-stain electron microscopy and mass photometry provided evidence for both intra- and inter-spike crosslinking. This study highlights the utility of cross-neutralizing antibodies for designing bivalent or multivalent agents to provide a robust activity against circulating variants, as well as future SARS-like coronaviruses.

immunology↗

bioRxiv2022

Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies

SummaryLassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences amongst LASV lineages. Despite the sequence diversity of GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VI, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of GPC in complex with GP1-A antibodies reveal their neutralization mechanisms. Finally, we present the isolation and characterization of a novel trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines. HighlightsO_LIStructural characterization of soluble glycoproteins from four Lassa virus lineages. C_LIO_LIMAb 12.1F, belonging to the GP1-A cluster, inhibits matriglycan and LAMP-1 binding. C_LIO_LIGP1-A mAbs show glycan-dependence with 19.7E demonstrating lineage-dependent binding. C_LIO_LIA novel trimer-preferring NAb S370.7 targets the GPC-B epitope. C_LI

immunology↗