Differential Antibody-Based Immune Response Against Isolated GP1 Receptor-Binding Domains from Lassa and Junín Viruses

There are two predominant subgroups in the Arenaviridae family of viruses, the Old-World and the New-World viruses that use distinct cellular receptors for entry. While New-World viruses typically elicit good neutralizing antibody responses, the Old-World viruses generally evade such responses. Antibody based immune responses are directed against the glycoprotein spike complexes that decorate the viruses. A thick coat of glycans reduces the accessibility of antibodies to the surface of spike complexes from Old-World viruses but other mechanisms may further hamper the development of efficient humoral responses. Specifically, it was suggested that the GP1 receptor-binding module of the Old-World Lassa virus might help evading humoral response. Here we investigate the immunogenicity of the GP1 domain from Lassa virus and compare it to GP1 domain from the New-World Junin virus. We found striking differences in the ability of antibodies that were developed against these immunogens to target the same GP1 receptor-binding domains in the context of the native spike complexes. Whereas GP1 from Junin virus elicited productive neutralizing responses, GP1 from Lassa virus elicited only non-productive responses. These differences can be rationalized by conformational changes that GP1 from Lassa virus but not from Junin virus, undergoes after dissociating from the trimeric spike complex. Hence shedding of GP1 in the case of Lassa virus can indeed serve as a mechanism to subvert the humoral immune response. Moreover, the realization of using a recombinant protein for eliciting productive response against the New-World Junin virus may suggests a novel and safe way to design future vaccines. IMPORTANCE Some viruses that belong to the Arenaviridae family like Lassa and Junin viruses are notorious human pathogens, which may lead to fatal outcomes when they infect people. It is thus important to develop means to combat these viruses. For developing effective vaccines, it is vital to understand the basic mechanisms that these viruses utilize in order to evade or overcome host immune responses. It was previously noted that the GP1 receptor-binding domain from Lassa virus is shedded and accumulates in the sera of infected individuals. This raised the possibility that Lassa GP1 may function as an immunological decoy. Here we demonstrate that mice develop non-productive immune responses against GP1 from Lassa virus, which is in contrast to effective neutralizing responses that GP1 from Junin virus elicits. Thus, GP1 from Lassa virus is indeed an immunological decoy and GP1 from Junin virus may serve as a constituent of a future vaccine.