A MOPEVAC multivalent vaccine induces sterile protection against New World arenaviruses in non-human primates

Vaccine Candidates against Arenavirus Infections

“…Indeed, recombinant LASV, MOPV or PICV with mutations in the active site of the ExoN domain cause higher IFN-I responses compared to wild-type recombinant viruses. It should be noted that such recombinant viruses with mutations in the ExoN domain are investigated as vaccine candidates [ 32 , 33 , 34 ]. JUNV NP has also been revealed to contain the DEDDh motif; however, it is considered incomplete without ExoN activity.…”

“…Several vaccine candidates against LF have been developed [ 46 , 47 ]. Three vaccine candidates, the recombinant vesicular stomatitis virus (VSV) expressing LASV GPC (rVSV∆G-LASV-GPC) [ 50 , 51 , 52 ], the recombinant measles virus expressing LASV GPC and NP (MV-LASV) [ 34 , 53 ], and a DNA vaccine encoding the LASV GPC gene (INO-4500) [ 54 ] have been evaluated for their safety and efficacy in phase 1 clinical trials (IAVI C102 : NCT04794218, V182-001 : NCT04055454, and LSV-001 : NCT03805984, respectively). The results of these studies are not yet available.…”

“…Several vaccine candidates, such as replication-incompetent virus vectors, inactivated LASV, virus-like particles, and DNA vaccines, have demonstrated some effectiveness ( Table 1 ) [ 4 , 58 ]. Among these, some candidates using replication-competent virus vectors have succeeded with high protective efficacy and immunogenicity, and are in further development as remarkable vaccine candidates [ 34 , 50 , 51 , 52 , 53 ].…”

“…A recombinant measles virus (Schwarz strain) vaccine candidate expressing both the LASV GPC and NP (MV-LASV) induces efficient protection against homologous LASV challenge after a single administration in cynomolgus macaques [ 34 ]. This vaccine candidate induces long-term immunity and protects against heterologous LASV strain challenge in this animal model [ 53 ].…”

“…Although its immune induction properties and protective effect for MACV, GTOV, and CHAPV infections are still unclear, r3MACV might be a strong candidate as a pan-NW arenavirus vaccine. MOPEVAC expressing MACV GPC (MOPEVAC MACV ) and the pentavalent MOPEVAC vaccine candidate expressing GPCs from all pathogenic South American NW arenaviruses (MOPEVAC NEW ) induce cross-neutralizing antibodies against JUNV in cynomolgus macaques after boost immunization [ 34 ].…”