Combination of highly antigenic nucleoproteins to inaugurate a cross-reactive next generation vaccine candidate against Arenaviridae family

Abstract

Arenaviral infections often result lethal hemorrhagic fevers, affecting primarily in African and South American regions. To date, there is no FDA-approved licensed vaccine against arenaviruses and treatments have been limited to supportive therapy. Hence, the study was employed to design a highly immunogenic cross-reactive vaccine against Arenaviridae family using reverse vaccinology approach. The whole proteome of Lassa virus (LASV), Lymphocytic Choriomeningitis virus (LCMV), Lujo virus and Guanarito virus were retrieved and assessed to determine the most antigenic viral proteins. Both T-cell and B-cell epitopes were predicted and screened based on transmembrane topology, antigenicity, allergenicity, toxicity and molecular docking analysis. The final constructs were designed using different adjuvants, top epitopes, PADRE sequence and respective linkers and were assessed for the efficacy, safety, stability and molecular cloning purposes. The proposed epitopes were highly conserved (84%-100%) and showed greater cumulative population coverage. Moreover, T cell epitope GWPYIGSRS was conserved in Junin virus (Argentine mammarenavirus) and Sabia virus (Brazilian mammarenavirus), while B cell epitope NLLYKICLSG was conserved in Machupo virus (Bolivian mammarenavirus) and Sabia virus, indicating the possibility of final vaccine construct to confer a broad range immunity in the host. Docking analysis of the refined vaccine with different MHC molecules and human immune receptors were biologically significant. The vaccine-receptor (V1-TLR3) complex showed minimal deformability at molecular level and was compatible for cloning into pET28a(þ) vector of E. coli strain K12. The study could be helpful in developing vaccine to combat arenaviral infections in the future. However, further in vitro and in vivo trials using model animals are highly recommended for the experimental validation of our findings.

Core Proteomics and Immunoinformatic Approaches to Design a Multiepitope Reverse Vaccine Candidate against Chagas Disease

“…A PEPFOLD server was used to convert 16 T-cell epitopes (8 CTL and 8 HTL) into 3D structures, and their interactions with HLA molecules were investigated. The top epitopes were docked against class-I and class-II alleles [ 80 ]. According to the findings, all the anticipated epitopes are bound in the groove of MHC molecules with suitable binding energy ( Table 5 ).…”

Combining segments 9 and 10 in DNA and recombinant protein vaccines conferred superior protection against tilapia lake virus in hybrid red tilapia (oreochromis sp.) compared to single segment vaccines

“…With specific antibody production to protect against TiLV in tilapia, the synergistic effect of protein immunogenic properties might result from the combination of the number of B-cell epitopes, the alignment of amino acids in the epitope and their secondary structure. Selection of antigenic proteins or epitopes for rationale vaccine design should include 1) overall structure as > 40% coil structure ( 60 – 64 ), 2) > 50% amino acid residues exposed to the surface ( 61 ) and 3) a large number of total surface exposed B-cell epitope residues in coil formation ( 61 ).…”

An updated review and current challenges of Guanarito virus infection, Venezuelan hemorrhagic fever

“…Currently, there is no FDA-approved vaccine for any pathogenic arenavirus. In Argentina, the live attenuated Candid#1 vaccine of JUNV has been shown to be effective in preventing Argentine hemorrhagic fever, and monoclonal antibodies produced from Candid#1-immunized humans neutralize MACV [ 56 , 57 ]. However, the effectiveness of Candid#1 immunity for prevention of MACV infection is still not clear, as it failed to prevent lethal MACV infection in a mouse model [ 58 ].…”

“…However, the effectiveness of Candid#1 immunity for prevention of MACV infection is still not clear, as it failed to prevent lethal MACV infection in a mouse model [ 58 ]. Furthermore, the effectivity of Candid#1 as a preventive measure against other arenaviruses, including GTOV, has not yet been investigated [ 56 ].…”

“…Some epitopes on viral proteins have shown a lack of cross-reactivity with different arenaviruses, but there are some small antigenic sites that have been shown to be very conserved among many arenaviruses, making them possible molecular targets for vaccines [ 6 ]. Recently, a study based on genome and immune informatics showed that the viral NP can be a potential target for designing a cross-reactive vaccine against pathogenic arenaviruses, since NP can stimulate a humoral and cell-mediated immune response [ 56 ].…”