Potent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responses.
Por:
Beltran-Pavez C, Bontjer I, Gonzalez N, Pernas M, Merino-Mansilla A, Olvera A, Miro JM, Brander C, Alcami J, Sanders RW, Sanchez-Merino V and Yuste E
Publicada:
12 ene 2022
Ahead of Print:
20 oct 2021
Resumen:
Longitudinal studies in HIV-1-infected individuals have indicated that 2 to 3 years of infection are required to develop broadly neutralizing antibodies. However, we have previously identified individuals with broadly neutralizing activity (bNA) in early HIV-1 infection, indicating that a vaccine may be capable of bNA induction after short periods of antigen exposure. Here, we describe 5 HIV-1 envelope sequences from individuals who have developed bNA within the first 100 days of infection (early neutralizers) and selected two of them to design immunogens based on HIV-1-Gag virus-like particles (VLPs). These VLPs were homogeneous and incorporated the corresponding envelopes (7 to 9 µg of gp120 in 10(10) VLPs). Both envelopes (Envs) bound to well-characterized broadly neutralizing antibodies (bNAbs), including trimer-specific antibodies (PGT145, VRC01, and 35022). For immunogenicity testing, we immunized rabbits with the Env-VLPs or with the corresponding stabilized soluble envelope trimers. A short immunization protocol (105 days) was used to recapitulate the early nAb induction observed after HIV-1 infection in these two individuals. All VLP and trimeric envelope immunogens induced a comparably strong anti-gp120 response despite having immunized rabbits with 30 times less gp120 in the case of the Env-VLPs. In addition, animals immunized with VLP-formulated Envs induced antibodies that cross-recognized the corresponding soluble stabilized trimer and vice versa, even though no neutralizing activity was observed. Nevertheless, our data may provide a new platform of immunogens, based on HIV-1 envelopes from patients with early broadly neutralizing responses, with the potential to generate protective immune responses using vaccination protocols similar to those used in classical preventive vaccines. IMPORTANCE It is generally accepted that an effective HIV-1 vaccine should be able to induce broad-spectrum neutralizing antibodies. Since most of these antibodies require long periods of somatic maturation in vivo, several groups are developing immunogens, based on the HIV envelope protein, that require complex and lengthy immunization protocols that would be difficult to implement in the general population. Here, we show that rabbits immunized with new envelopes (VLP formulated) from two individuals who demonstrated broadly neutralizing activity very early after infection induced specific HIV-1 antibodies after a short immunization protocol. This evidence provides the basis for generating protective immune responses with classic vaccination protocols with vaccine prototypes based on HIV envelope sequences from individuals who have developed early broadly neutralizing responses.
Filiaciones:
Beltran-Pavez C:
Institute of Health Carlos III, ISCIII, National Microbiology Centre, Madrid, Spain
University of Barcelona, Faculty of Pharmacy and Food Science, Barcelona, Spain
Bontjer I:
Department of Medical Microbiology, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Gonzalez N:
Institute of Health Carlos III, ISCIII, National Microbiology Centre, Madrid, Spain
Pernas M:
Institute of Health Carlos III, ISCIII, National Microbiology Centre, Madrid, Spain
Merino-Mansilla A:
Institute of Health Carlos III, ISCIII, National Microbiology Centre, Madrid, Spain
:
IrsiCaixa, AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain
Universitat de Vic-Universitat Central de Catalunya, Vic, Spain
Miro JM:
Infectious Diseases Service, Hospital Clinic-IDIBAPS. University of Barcelona, Barcelona, Spain
:
IrsiCaixa, AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain
Universitat de Vic-Universitat Central de Catalunya, Vic, Spain
ICREA, Barcelona, Spain
Alcami J:
Institute of Health Carlos III, ISCIII, National Microbiology Centre, Madrid, Spain
Infectious Diseases Service, Hospital Clinic-IDIBAPS. University of Barcelona, Barcelona, Spain
Sanders RW:
Department of Medical Microbiology, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, USA
Sanchez-Merino V:
Institute of Health Carlos III, ISCIII, National Microbiology Centre, Madrid, Spain
Yuste E:
Institute of Health Carlos III, ISCIII, National Microbiology Centre, Madrid, Spain
Green Published
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