tetano
Editor, Senior Moderator
Nat Commun
. 2025 Jun 3;16(1):5162.
doi: 10.1038/s41467-025-60481-2. Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response
Kenta Matsuda[SUP] 1 [/SUP], Mitra Harrison[SUP] 1 [/SUP], Eleanor Wettstein[SUP] 1 [/SUP], Jessica Pederson[SUP] 1 [/SUP], Alyssa A Pullano[SUP] 1 [/SUP], Lyuba Bolkhovitinov[SUP] 1 [/SUP], Breanna Kim[SUP] 1 [/SUP], Isabel Steinberg[SUP] 1 [/SUP], Trevor Griesman[SUP] 1 [/SUP], Sarah Stuccio[SUP] 1 [/SUP], Daniel Rogan[SUP] 1 [/SUP], Andy Patamawenu[SUP] 1 [/SUP], Tulley Shofner[SUP] 1 [/SUP], Nathaniel E Wright[SUP] 1 [/SUP], Jonathan D Webber[SUP] 1 [/SUP], Freya Van't Veer[SUP] 1 [/SUP], Rachel Roenicke[SUP] 1 [/SUP], Emma Koory[SUP] 1 [/SUP], Peyton M Roeder[SUP] 1 [/SUP], Ellison Ober[SUP] 1 [/SUP], Benjamin Leach[SUP] 1 [/SUP], Yaroslav Tsybovsky[SUP] 2 [/SUP], Tyler Stephens[SUP] 2 [/SUP], Ivan Del Moral-Sanchez[SUP] 3 [/SUP], Ilja Bontjer[SUP] 3 [/SUP], Lori W McGinnes-Cullen[SUP] 4 [/SUP], Eric Chu[SUP] 5 [/SUP], Jason Liang[SUP] 5 [/SUP], Jonathan L Torres[SUP] 6 [/SUP], Ryan N Lin[SUP] 6 [/SUP], Andy S Tran[SUP] 6 [/SUP], Gabrielle Dziubla[SUP] 7 [/SUP], Leonid Serebryannyy[SUP] 7 [/SUP], Sandeep Narpala[SUP] 7 [/SUP], Bob Lin[SUP] 7 [/SUP], Mike Castro[SUP] 7 [/SUP], Gabriel Ozorowski[SUP] 6 [/SUP], Andrew B Ward[SUP] 6 [/SUP], Rogier W Sanders[SUP] 3 [/SUP], Peter D Kwong[SUP] 7 [/SUP], Javier Guenaga[SUP] 8 [/SUP], Richard Wyatt[SUP] 8 [/SUP], Trudy Morrison[SUP] 4 [/SUP], Mark Connors[SUP] 9 [/SUP]
Affiliations
HIV-1 Env glycoprotein (Env) immunogenicity is limited in part by structural instability and extensive glycan shielding and is likely the greatest obstacle to an HIV-1 vaccine. Stabilized Env trimers can elicit serum neutralizing antibodies, but the response is short-lived. Here we use Newcastle Disease Virus-like particle (NDV-VLP) platform to present stabilized versions of HIV-1 Env at high valency and in the context of varied conformational stability, adjuvants, dose, and antigen persistence. Influenza virus hemagglutinin, or SARS-CoV2 Spike-bearing VLPs rapidly induce neutralizing antibodies, in contrast, they were not induced by those bearing Env. A replicating adenovirus type 4 expressing Env rapidly induces autologous neutralizing antibodies. However, durable neutralizing antibodies are induced only when multiple features of a replicating virus infection are combined, with the largest impact from dose and escalating dose. In summary, we show here immunogenicity of HIV-1 Env could be improved by reproducing features of virus infection.
. 2025 Jun 3;16(1):5162.
doi: 10.1038/s41467-025-60481-2. Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response
Kenta Matsuda[SUP] 1 [/SUP], Mitra Harrison[SUP] 1 [/SUP], Eleanor Wettstein[SUP] 1 [/SUP], Jessica Pederson[SUP] 1 [/SUP], Alyssa A Pullano[SUP] 1 [/SUP], Lyuba Bolkhovitinov[SUP] 1 [/SUP], Breanna Kim[SUP] 1 [/SUP], Isabel Steinberg[SUP] 1 [/SUP], Trevor Griesman[SUP] 1 [/SUP], Sarah Stuccio[SUP] 1 [/SUP], Daniel Rogan[SUP] 1 [/SUP], Andy Patamawenu[SUP] 1 [/SUP], Tulley Shofner[SUP] 1 [/SUP], Nathaniel E Wright[SUP] 1 [/SUP], Jonathan D Webber[SUP] 1 [/SUP], Freya Van't Veer[SUP] 1 [/SUP], Rachel Roenicke[SUP] 1 [/SUP], Emma Koory[SUP] 1 [/SUP], Peyton M Roeder[SUP] 1 [/SUP], Ellison Ober[SUP] 1 [/SUP], Benjamin Leach[SUP] 1 [/SUP], Yaroslav Tsybovsky[SUP] 2 [/SUP], Tyler Stephens[SUP] 2 [/SUP], Ivan Del Moral-Sanchez[SUP] 3 [/SUP], Ilja Bontjer[SUP] 3 [/SUP], Lori W McGinnes-Cullen[SUP] 4 [/SUP], Eric Chu[SUP] 5 [/SUP], Jason Liang[SUP] 5 [/SUP], Jonathan L Torres[SUP] 6 [/SUP], Ryan N Lin[SUP] 6 [/SUP], Andy S Tran[SUP] 6 [/SUP], Gabrielle Dziubla[SUP] 7 [/SUP], Leonid Serebryannyy[SUP] 7 [/SUP], Sandeep Narpala[SUP] 7 [/SUP], Bob Lin[SUP] 7 [/SUP], Mike Castro[SUP] 7 [/SUP], Gabriel Ozorowski[SUP] 6 [/SUP], Andrew B Ward[SUP] 6 [/SUP], Rogier W Sanders[SUP] 3 [/SUP], Peter D Kwong[SUP] 7 [/SUP], Javier Guenaga[SUP] 8 [/SUP], Richard Wyatt[SUP] 8 [/SUP], Trudy Morrison[SUP] 4 [/SUP], Mark Connors[SUP] 9 [/SUP]
Affiliations
- PMID: 40461490
- DOI: 10.1038/s41467-025-60481-2
HIV-1 Env glycoprotein (Env) immunogenicity is limited in part by structural instability and extensive glycan shielding and is likely the greatest obstacle to an HIV-1 vaccine. Stabilized Env trimers can elicit serum neutralizing antibodies, but the response is short-lived. Here we use Newcastle Disease Virus-like particle (NDV-VLP) platform to present stabilized versions of HIV-1 Env at high valency and in the context of varied conformational stability, adjuvants, dose, and antigen persistence. Influenza virus hemagglutinin, or SARS-CoV2 Spike-bearing VLPs rapidly induce neutralizing antibodies, in contrast, they were not induced by those bearing Env. A replicating adenovirus type 4 expressing Env rapidly induces autologous neutralizing antibodies. However, durable neutralizing antibodies are induced only when multiple features of a replicating virus infection are combined, with the largest impact from dose and escalating dose. In summary, we show here immunogenicity of HIV-1 Env could be improved by reproducing features of virus infection.