Cross-Protection against Challenge with Puumala Virus after Immunization with Nucleocapsid Proteins from Different Hantaviruses

Abstract

Hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome in humans. The nucleocapsid protein (N) is relatively conserved among hantaviruses and highly immunogenic in both laboratory animals and humans, and it has been shown to induce efficient protective immunity in animal models. To investigate the ability of recombinant N (rN) from different hantaviruses to elicit cross-protection, we immunized bank voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized with PUUV and TOPV rN were completely protected. In the group immunized with DOBV rN, 7 of 10 animals were protected, while only 3 of 8 animals were protected in the group immunized with ANDV rN, which is more closely related to PUUV rN than DOBV rN. Humoral and cellular immune responses after rN immunization were also investigated. The highest cross-reactive humoral responses against PUUV antigen were detected in sera from ANDV rN-immunized animals, followed by those from TOPV rN-immunized animals, and only very low antibody cross-reactivity was observed in sera from DOBV rN-immunized animals. In proliferation assays, T lymphocytes from animals immunized with all heterologous rNs were as efficiently recalled in vitro by PUUV rN as were T lymphocytes from animals immunized with homologous protein. In summary, this study has shown that hantavirus N can elicit cross-protective immune responses against PUUV, and the results suggest a more important role for the cellular arm of the immune response than for the humoral arm in cross-protection elicited by rN.

Human pathogenic hantaviruses and prevention of infection

“…64 Moreover, in bank voles vaccination with recombinant N proteins from PUUV and other hantaviruses induces protection and even cross-protection against PUUV that is based on T-cell responses rather than production of neutralizing antibodies. 47,65,66 Collectively, these findings underline the importance of cellular immunity for protection from hantavirus infection.…”

“…47 Collectively, these results demonstrate the feasibility to generate vaccines that protect against multiple hantavirus types.…”

Identification of Three Novel CTL Epitopes within Nucleocapsid Protein of Hantaan Virus

“…In this study, we focused our investigations on the HTNV nucleocapsid protein, which has been shown to induce efficient protection against virus challenge in animal models (1,2,9), and stronger IFN-c-producing T-cell responses in patients with milder HFRS than in those with severe disease (22), because we were unable to collect enough blood samples from patients to study the T-cell responses to peptide antigens spanning the entire genome. We have analyzed the nucleocapsid-specific T-cell response in two HTNV-infected donors.…”

Treatment of hantavirus pulmonary syndrome

“…Distribution is unlimited. voles) for both Old-World and New-World viruses (Dargeviciute et al, 2002;de Carvalho Nicacio et al, 2002;Klingstrom et al, 2004;Maes et al, 2006;Lindkvist et al, 2007;Geldmacher et al, 2005). In addition, a SNV S gene-based DNA vaccine and a Puumala truncated S gene-based DNA vaccine demonstrated some protective efficacy in the deer mouse or bank vole models (2 of 5 animals), respectively (Bharadwaj et al, 2002;Bucht et al, 2001).…”