Immunization with a Self-Assembled Nanoparticle Vaccine Elicits Potent Neutralizing Antibody Responses against EBV Infection

Abstract

Epstein–Barr virus (EBV) infection is a global health concern infecting over 90% of the population. However, there is no currently available vaccine. EBV primarily infects B cells, where the major glycoprotein 350 (gp350) is the main target of neutralizing antibodies. Given the advancement of nanoparticle vaccines, we describe rationally designed vaccine modalities presenting 60 copies of gp350 on self-assembled nanoparticles in a repetitive array. In a mouse model, gp350s on lumazine synthase (LS) and I3-01 adjuvanted with MF59 or aluminum hydroxide (Alhydrogel) elicited over 65- to 133-fold higher neutralizing antibody titers than the corresponding gp350 monomer to EBV. Furthermore, immunization with gp350D123-LS and gp350D123-I3-01 vaccine induced a Th2-biased response. For the nonhuman primate model, gp350D123-LS in MF59 elicited higher titers of total IgG and neutralizing antibodies than the monomeric gp350D123. Overall, these results support gp350D123-based nanoparticle vaccine design as a promising vaccine candidate for potent protection against EBV infection.

Stress-Induced Epstein-Barr Virus Reactivation

“…In addition, injecting Cynomolgus macaques with gp350D 123 -LS resulted in higher antibody titers than gp350D 123 . Nanoparticles combined with the adjuvant MF59 stimulated a more robust humoral response than nanoparticles combined with the adjuvant aluminum hydroxide [ 203 ].…”

Main Targets of Interest for the Development of a Prophylactic or Therapeutic Epstein-Barr Virus Vaccine

“…Lastly, Kang et al (2021) demonstrated the immunogenicity of the first 425 residues of the gp350/220 ectodomain expressed on two different self-assembled nanoparticles that mimic the shape and size of EBV: lumazine synthase (LS) and I3-01, two capsid-forming enzymes. The gp350/220 1−425 -LS and gp350/220 1−425 -I3-01 nanoparticles adjuvanted with aluminum hydroxide or MF59 elicited in mice over 133-and 65-fold higher neutralizing antibody titers, respectively, than that induced by the corresponding gp350 monomer (Kang et al, 2021). Cui et al, 2013;1b, Kanekiyo et al, 2015;1c, Zhao et al, 2018;1d, Zhang et al, 2020;1e, Kang et al, 2021;2a,2b, Cui et al, 2016;2c, Cui et al, 2021;2d, Bu et al, 2019;2e, Escalante et al, 2020;3, Elliott et al, 2008;4a,4b, Perez et al, 2017;4c, van Zyl et al, 2018. While these new strategies have yet to be compared with one another, all of them seem to be more immunogenic than soluble gp350 monomers and represent promising attempts to enhance the immunogenicity of anti-gp350/220 vaccines.…”

“… Optimization of prophylactic vaccine strategies. 1a, Cui et al, 2013 ; 1b, Kanekiyo et al, 2015 ; 1c, Zhao et al, 2018 ; 1d, Zhang et al, 2020 ; 1e, Kang et al, 2021 ; 2a,2b, Cui et al, 2016 ; 2c, Cui et al, 2021 ; 2d, Bu et al, 2019 ; 2e, Escalante et al, 2020 ; 3, Elliott et al, 2008 ; 4a,4b, Perez et al, 2017 ; 4c, van Zyl et al, 2018 . …”

“…Lastly, Kang et al (2021) demonstrated the immunogenicity of the first 425 residues of the gp350/220 ectodomain expressed on two different self-assembled nanoparticles that mimic the shape and size of EBV: lumazine synthase (LS) and I3-01, two capsid-forming enzymes. The gp350/220 1 – 425 -LS and gp350/220 1 – 425 -I3-01 nanoparticles adjuvanted with aluminum hydroxide or MF59 elicited in mice over 133- and 65-fold higher neutralizing antibody titers, respectively, than that induced by the corresponding gp350 monomer ( Kang et al, 2021 ).…”

Vesicular Stomatitis Virus-Based Epstein-Barr Virus Vaccines Elicit Strong Protective Immune Responses

“…Thus, it is reasonable to make gp350 the primary target for vaccine development ( 11 ). By incorporating gp350 into different forms of carriers, such as monomers ( 12 ), oligomers ( 13 , 14 ), nanoparticles ( 15 , 16 ), vaccinia viruses ( 17 ), recombinant adenoviruses ( 18 ), varicella-zoster viruses (VZVs) ( 19 ), and Newcastle disease viruses (NDVs) ( 20 , 21 ), many gp350-centered vaccines have emerged. To date, however, clinical trials of gp350-centered vaccines have shown no protection against EBV infection ( 22 ).…”