Kubinski et al.
Cross-reactive antibodies against Langat virus protect mice from lethal tick-borne encephalitis virus infection
Front Immunol. 2023;14:1134371. doi:10.3389/fimmu.2023.1134371

Langat virus (LGTV) is a flavivirus occurring in southeast Asia. It belongs to the TBE serocomplex and with TBE virus, it shares greater than 80% amino acid identity in the glycoprotein E (gE). No clinical cases of disease caused by LGTV have so far been reported in humans. Vaccine development approaches based on attenuated LGTV and carried out in the 1970s were discontinued. In a recent study, the contribution of cross-reactive antibodies and T cells specific for LGTV against lethal TBE virus infection in mice have been studied.

Subcutaneous administration of LGTV resulted in the production of cross-reactive and neutralizing antibodies directed to gE and the non-structural protein 1 (NS-1) and could protect mice against subsequent challenge with TBE virus. Also, a high frequency of CD4+ T cells that specifically cross-reacted with epitopes within gE, NS3 and NS5 was observed.

Passive immunization of mice with LGTV-specific serum could partially protect mice against disease upon TBE virus infection, and no virus was observed in serum and spleen.

All mice that received T cells either from controls or from LGTV-infected mice developed severe illness and had high viral load in the brain and spinal cord showing that T cells cannot control infection in the absence of serum antibodies. Histopathological changes were greater in controls than in mice receiving serum from LGTV-infected donors, and perivascular inflammation scores differed significantly between control-serum and LGTV-serum group, and mice did not show significant pathological lesions within the gastrointestinal tract.

The authors discussed that gE and NS1 antibodies induced by LGTV infection may be contributing to cross-protective immunity against TBE virus infection. T cells from LGTV-infected mice responded to TBE virus antigens; however, adoptive transfer of T cells from LGTV-infected donor mice failed to protect naïve mice from subsequent challenge with TBE virus, but these T cells may contribute to pathological changes.

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