Humoral and cellular immune responses to Lassa fever virus in Lassa fever survivors and their exposed contacts in Southern Nigeria

Abstract

Elucidating the adaptive immune characteristics of natural protection to Lassa fever (LF) is vital in designing and selecting optimal vaccine candidates. With rejuvenated interest in LF and a call for accelerated research on the Lassa virus (LASV) vaccine, there is a need to define the correlates of natural protective immune responses to LF. Here, we describe cellular and antibody immune responses present in survivors of LF (N = 370) and their exposed contacts (N = 170) in a LASV endemic region in Nigeria. Interestingly, our data showed comparable T cell and binding antibody responses from both survivors and their contacts, while neutralizing antibody responses were primarily seen in the LF survivors and not their contacts. Neutralizing antibody responses were found to be cross-reactive against all five lineages of LASV with a strong bias to Lineage II, the prevalent strain in southern Nigeria. We demonstrated that both T cell and antibody responses were not detectable in peripheral blood after a decade in LF survivors. Notably LF survivors maintained high levels of detectable binding antibody response for six months while their contacts did not. Lastly, as potential vaccine targets, we identified the regions of the LASV Glycoprotein (GP) and Nucleoprotein (NP) that induced the broadest peptide-specific T cell responses. Taken together this data informs immunological readouts and potential benchmarks for clinical trials evaluating LASV vaccine candidates.

Immunological insights into COVID-19 in Southern Nigeria

“…Here we extended these observations to demonstrate that sera from asymptomatic participants neutralized SARS-CoV-2 Spike PVs to the same level as sera from symptomatic COVID-19 survivors. This contrasted our observation in Lassa fever disease immunity where both hospitalized and non hospitalized patients generate binding antibody response to the Lassa virus GP and NP protein but neutralizing antibody response was mainly from the hospitalized patients ( 21 ). The binding antibody response to N antigens observed in both sera from symptomatic and asymptomatic individuals needs to be differentiated by peptide-based assays to determine if the antibody response is from SARS-CoV- related or other Coronaviruses.…”

The Adaptive Immune Response against Bunyavirales

“…Beyond studies involving LCMV, T cell responses against LASV and other mammarenaviruses have also been characterized [ 58 , 59 , 60 , 133 ]. These studies focused on identifying immunogenic epitopes against entire proteomes for several mammarenavirus strains (LASV, LUJV, CHAPV, JUNV, MACV, GTOV, and SABV), with the goal of identifying conserved epitopes among the family [ 58 , 133 , 134 , 135 ].…”

“…Immunoinformatic analysis identified several highly immunogenic epitopes, mostly all located in conserved regions of GPC and N [ 58 ]. Ex vivo stimulation of LF survivor cells narrowed down the panel of immunodominant epitopes to 12 CD8+ T cell-positive epitopes within GPC and N which induced broad peptide-specific T cell responses, supported by predictive HLA-binding algorithms ( Table 1 ) [ 59 , 60 ]. Further, four immunodominant CD4+ T cell epitopes, which are highly conserved between Old and New World arenaviruses, were identified and mainly localized to a short stretch of 13 amino acids located in the N-terminal part of GP2 (289–301) ( Table 1 ) [ 61 ].…”

The Adaptive Immune Response against Bunyaviruses

“…Beyond studies involving LCMV, T cell responses against LASV and other mammarenaviruses have also been characterized [58][59][60]133]. These studies focused on identifying immunogenic epitopes against entire proteomes for several mammarenavirus strains (LASV, LUJV, CHAPV, JUNV, MACV, GTOV, and SABV), with the goal of identifying conserved epitopes among the family [58, [133][134][135].…”

“…Immunoinformatic analysis identified several highly immunogenic epitopes, mostly all located in conserved regions of GPC and N [58]. Ex vivo stimulation of LF survivor cells narrowed down the panel of immunodominant epitopes to 12 CD8+ T cell-positive epitopes within GPC and N which induced broad peptide-specific T cell responses, supported by predictive HLA-binding algorithms (Table 1) [59,60]. Further, four immunodominant CD4+ T cell epitopes, which are highly conserved between Old and New World arenaviruses, were identified and mainly localized to a short stretch of 13 amino acids located in the N-terminal part of GP2 (289-301) (Table 1) [61].…”