Protection against respiratory syncytial virus (RSV) elicited in mice by plasmid DNA immunisation encoding a secreted RSV G protein-derived antigen

Abstract

Plasmid vectors encoding two different variants, one cytoplasmic and one secreted version, of a candidate vaccine BBG2Na to respiratory syncytial virus (RSV), were constructed and evaluated in a nucleic acid vaccination study. The two different vectors, which employed the Semliki Forest virus gene amplification system, were found to express BBG2Na appropriately in in vitro cell cultures. Immunisation of mice with the plasmid vectors elicited significant serum anti-BBG2Na IgG responses only in the mice receiving the plasmid encoding the secreted version of BBG2Na. Consistent with antibody induction data, sterilising lung protection against RSV-A challenge was also only observed in this group. These results indicate that the targeting of antigen expression (intracellular versus secreted) would be an important factor to consider in the design of nucleic acid vaccines.

DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice

“…The alphavirus-based replicon platform technology has been developed as vaccine candidates towards many different infectious diseases, including vaccines for influenza A virus (IAV) 41 , respiratory syncytial virus (RSV) 42,43 , Ebola (EBOV), hepatitis C virus (HCV), chikungunya (CHIKV, now in phase III) 28,44 , HIV (now in phase I), human papilloma virus (HPV, now in therapeutic phase II) 45 . Given the generic design of our platform and that new constructs can be made rapidly with synthetic design of the insert, it can be readily adapted to SARS-CoV-2.…”

Respiratory Viral Vaccines

“…Finally, any candidate vaccine for RSV will need to be carefully evaluated to ensure that it does not cause the disease enhancement on primary exposure to wild-type virus that was associated with formalininactivated vaccine (Kapikian et al, 1969). Although there is no vaccine currently licensed for RSV, a variety of vaccine development strategies have been assessed, including those involving peptide (Jiang et al, 2002), subunit (Simoes et al, 2002;Goetsch et al, 2001;Power et al, 2001;Prince et al, 2000), virus vector (Dollenmaier et al, 2001;Schmidt et al, 2002), plasmid DNA/RNA (Andersson et al, 2000;Fleeton et al, 2001), and live attenuated vaccines Crowe et al, 1999;Wright et al, 2000).…”

Human immunoglobulin A (IgA)‐specific ligands from combinatorial engineering of protein A

“…Employing a 58-aminoacid domain derived from one of the immunoglobulin binding (IgG) domains of staphylococcal protein A as a scaffold, we have previously described the construction of combinatorial protein libraries from which novel affinity proteins (denoted Z-affibodies) have been selected for binding to desired target proteins using phage display technology [21,22]. In common with their protein A ancestor, several of the described affibodies have been shown to be useful as selective and robust ligands in affinity chromatography applications [23][24][25]. Here, we describe the use of the affibody technology platform for the identification of protein A-derived variants showing IgA-rather than IgG-binding, thus expanding the available repertoire of tools for detection and recovery of native or recombinant IgA from different sources.…”