Adjuvant formulated virus-like particles expressing native-like forms of the Lassa virus envelope surface glycoprotein are immunogenic and induce antibodies with broadly neutralizing activity

Abstract

Lassa mammarenavirus (LASV) is a rodent-borne arenavirus endemic to several West African countries. It is the causative agent of human Lassa fever, an acute viral hemorrhagic fever disease. To date, no therapeutics or vaccines against LASV have obtained regulatory approval. Polyclonal neutralizing antibodies derived from hyperimmunized animals may offer a useful strategy for prophylactic and therapeutic intervention to combat human LASV infections. The LASV envelope surface glycoprotein complex (GP) is the major target for neutralizing antibodies, and it is the main viral antigen used for the design of an LASV vaccine. Here, we assessed the immunogenic potential of mammalian cell-derived virus-like particles (VLPs) expressing GP from the prototypic LASV strain Josiah in a native-like conformation as the sole viral antigen. We demonstrate that an adjuvanted prime-boost immunization regimen with GP-derived VLPs elicited neutralizing antibody responses in rabbits, suggesting that effective antigenic epitopes of GP were displayed. Notably, these antibodies exhibited broad reactivity across five genetic lineages of LASV. VLP-based immunization strategies may represent a powerful approach for generating polyclonal sera containing cross-reactive neutralizing antibodies against LASV.

ChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal Lassa virus challenge

“…In a recent study, adjuvanted virus-like particles expressing a stable native-like LASV Josiah GP trimer induced the production of hyperimmune sera in rabbits with the capacity to neutralize multiple strains of LASV in vitro. It has yet to be determined if this system can induce sufficiently high titers of neutralizing antibodies to protect against LASV challenge in animal models 67 . Meanwhile, another study has suggested that non-neutralizing antibodies may play a role in controlling infection through antibody-dependent cellular phagocytosis or antibody-dependent cellular cytotoxicity 29 .…”

Humoral Immune Response in a Mouse Model Induced With Dengue Virus-like Particles Serotypes 1 and 4 Produced in Silkworm Larvae

“…).DENV-LPs/1CprME, /1prME, /4CprME, and /4prME could generate IgG antibody levels since many VLPs include structural or molecular characteristics that give certain auto-immunostimulatory qualities. These features enable VLPs to induce immunological responses without the use of adjuvants; nevertheless, adjuvants may enhance vaccination immunogenicity and encourage the activation of a speci c type of immune response when combined with VLP vaccines(Cimica and Galarza 2017;Donaldson et al 2018;Müller et al 2020). Our ITC data indicate that DENV-LP/1CPrME and DENV-LPs/4CPrME have a lower K D and ΔG than DENV-LP/1prME and DENV-LPs/4prME.…”

Advances in vaccine delivery systems against viral infectious diseases

“…Lass mammarenavirus-like protein nanoparticles were studied for the intramuscular delivery of the glycoprotein of Lassa mammarenavirus [46]. Lassa mammarenavirus is a rodent arenavirus that can cause acute hemorrhagic fever disease in humans [47].…”

“…The combination of nanovaccines with other adjuvant systems needs to be studied further. A few studies reported that enhanced immunogenicity was achieved by combining nanovaccines with commercial adjuvants [46], or codelivering nanovaccines with adjuvants in a nanomaterial. In cancer immunotherapy, the entrapment of various immune adjuvants (e.g., imiquimod) was found to enhance dendritic cells maturation and systemic immune responses [86].…”