Immunogenicity of a DNA-Based Sindbis Replicon Expressing Crimean–Congo Hemorrhagic Fever Virus Nucleoprotein

Crimean–Congo hemorrhagic fever virus (CCHFV) infrequently causes hemorrhagic fever in humans with a case fatality rate of 30%. Currently, there is neither an internationally approved antiviral drug nor a vaccine against the virus. A replicon based on the Sindbis virus vector encoding the complete open reading frame of a CCHFV nucleoprotein from a South African isolate was prepared and investigated as a possible candidate vaccine. The transcription of CCHFV RNA and recombinant protein production by the replicon were characterized in transfected baby hamster kidney cells. A replicon encoding CCHFV nucleoprotein inserted in plasmid DNA, pSinCCHF-52S, directed transcription of CCHFV RNA in the transfected cells. NIH-III heterozygous mice immunized with pSinCCHF-52S generated CCHFV IgG specific antibodies with notably higher levels of IgG2a compared to IgG1. Splenocytes from mice immunized with pSinCCHF-52S secreted IFN-γ and IL-2, low levels of IL-6 or IL-10, and no IL-4. No specific cytokine production was registered in splenocytes of mock-immunized mice (p < 0.05). Thus, our study demonstrated the expression of CCHFV nucleoprotein by a Sindbis virus vector and its immunogenicity in mice. The spectrum of cytokine production and antibody profile indicated predominantly Th1-type of an anti-CCHFV immune response. Further studies in CCHFV-susceptible animals are necessary to determine whether the induced immune response is protective.

piRNAs in the Olfactory Bulb Related to Fear Conditioning can Migrate from the Brain to the Germline

Small RNAs have been shown to be crucial in the mechanisms of transgenerational memory. Precisely, piRNAs have previously been thought to only exist in the germline and are related to transgenerational memory. To determine if the offspring inherits memory due to piRNA transmission, we conducted odor fear-conditioning tests and identified a piRNA that increased in abundance. That piRNA is thought to be involved in memory formation of the fear-conditioning test. We then used a virus vector to manipulate a single nucleotide of that piRNA sequence to see if it can migrate from the olfactory bulb to the germline. The data should theoretically indicate whether the mutant piRNA has migrated from the olfactory bulb to the germline of the mice.

Safety and Immunogenicity of a Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate, AVX/COVID-12-HEXAPRO (Patria), in Pigs

Several highly efficacious vaccines for SARS-CoV-2 have been developed and are used in the population. However, the current production capacity cannot meet the global demand. Therefore, additional vaccines—especially ones that can be produced locally and at low cost—are urgently needed. This work describes preclinical testing of a SARS-CoV-2 vaccine candidate which meets these criteria.