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SUMMARY Background: Classical swine fever (CSF) or hog cholera is a highly contagious and devastating disease of Suidae caused by an enveloped single-stranded RNA virus (CSFV) of the family Flaviviridae, genus Pestivirus. CSF has vast economic and trade significance all over the world, and it has the massive potential to spread rapidly from country to country. This is the reason why the World Organisation for Animal Health has listed CSF as a Notifiable Disease and it is also considered a transboundary animal disease.Objective: The objective of the present studies was to determine the efficacy of a single dose of a newly developed marker vaccine candidate against CSF, administered intramuscularly or orally in 6-week-old domestic piglets with and without maternally derived antibodies (MDAs) against Pestiviruses, to provide protection against a challenge with the highly virulent CSFV strain “Koslov” 14 days post vaccination. Materials and Methods: In both experiments two test groups were formed with 15 animals each, one group for intramuscular (im.), while another one for oral (p.o.) immunisation. The control groups contained 10 animals as unvac-cinated controls, respectively. All piglets were oronasally challenged with the highly virulent CSF virus (CSFV) strain “Koslov” 14 days post-vaccination. Results and Discussion: The vaccine candidate when administered im. provided complete protection in MDA- animals, while p.o. administration triggered only partial protection. Furthermore, we found that the presence of the MDAs had negative effect on the efficacy of the vaccine candidate. However, this was greatly influenced by the route of administration. Based on our observations, im. administration is recommended to achieve better immune response during the CSF control programs. The vaccine candidate met the criteria of Ph. Eur Mono-graph 0065, “Swine-fever vaccine (live, prepared in cell cultures), classical” 7th Edition. Fulfilling these validity criteria is a key step in the registration procedure for a vaccine candidate.

Summary The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies (bNAb) likely requires the appropriate presentation of stabilized trimers preventing exposure of non-neutralizing antibody (nNAb) epitopes. We designed a series of membrane-bound Envs with increased trimer stability through the introduction of key stabilization mutations. We derived a stabilized HIV-1 trimer, ConSOSL.UFO.750, which displays a dramatic reduction in nNAb binding while maintaining high quaternary and MPER-specific bNAb binding. Its soluble counterpart, ConSOSL.UFO.664, displays similar antigenicity, and its native-like Env structure is confirmed by negative stain-EM and glycosylation profiling of the soluble ConSOSL.UFO.664 trimer. A rabbit immunization study demonstrated that the ConSOSL.UFO.664 can induce autologous tier 2 neutralization. We have successfully designed a stabilized native-like Env trimer amenable to nucleic acid or viral vector-based vaccination strategies., Graphical Abstract, Highlights • DNA-expressed closed pre-fusion native-like Env with preserved MPER exposure • Env antigenicity varies across cell types and assays • Muscle cells present properly folded and glycosylated membrane-bound Envs • Fully glycosylated ConSOSL.UFO.664 induces autologous tier 2 neutralization, Aldon et al. developed membrane-bound and soluble stabilized HIV-1 Env trimer immunogens suitable for DNA/RNA or viral vector vaccines. The sequential iterative design and analysis in muscle cells have the potential to be used as a generalizable method for the expression of stabilized native-like trimers.