Current research for a vaccine against Lassa hemorrhagic fever virus

Warner, Bryce M; Safronetz, David; Stein, Derek R

The role of humoral immune responses during LASV infection has been debated more than that of T cells. Their correlation with survival has been difficult to determine due to the variability in antibody responses. IgM and IgG responses occur during LASV infection, but to a lesser degree than what might be expected for them to play a major role in protection from disease. Additionally, neutralizing antibodies against LASV are not produced in large quantities during infection due to the structural properties of the LASV GPC and its glycan shield, potentially limiting the role of the humoral response in protection. 21 Despite these issues, the importance of antibodies in protection against LASV may be understated. The vesicular stomatitis virus vaccine expressing LASV glycoprotein (VSV-LASV-GPC) is able to induce a strong humoral response against LASV GPC and provides similar protection to vaccines inducing strong T-cell responses. 28 The use of immune plasma and convalescent serum as a treatment for LASV infection in experimental models has shown mixed results, likely contributing to the skepticism of the protective ability of antibodies. [34] [35] [36] However, the use of human monoclonal antibodies in both guinea pig and NHP models of LF has shown to be protective. 37, 38 These monoclonal antibodies used for protection in both models have a high neutralizing index, providing evidence that perhaps a strong neutralizing response may be protective. The lack of neutralizing antibodies produced during natural infection may be the reason why no correlation between antibody production and survival has been observed. However, these animal models show that vaccine/therapeutic candidates are able to induce high neutralizing titers and may be feasible for protection against LASV.