Live attenuated viral vectors based on the rubella vaccine strain RA27/3

Abstract

Abstract We have developed a series of live viral vectors based on the live attenuated rubella vaccine strain RA27/3. These vectors can express a variety of heterologous vaccine antigens without interfering with vector growth or stable antigen expression. The vaccine inserts were expressed for at least 5 to 10 passages in Vero cells. Proteins as large as the ectodomain of HIV gp140 could be expressed (90 kDa), and they retained the native conformation. Recently expressed vaccine inserts include: P27 Gag protein of SIV, the NANP repeat sequence of malaria circumsporozoite protein, and the receptor binding domain of Sars CoV-2 S1 spike protein. We have studied these vectors for immunogenicity in a rhesus macaque model. The rubella vectors are based on the rubella vaccine strain, for which one or two doses can elicit lifelong immunity. The vectors are a little different: The best immune response was observed when the macaques were primed with a DNA vaccine, followed by rubella vectors, or when they were primed with rubella vector and then boosted with the native protein. In both cases, an immunization strategy with only one exposure to rubella antigens was better than giving it twice. This could occur if the secondary response to rubella antigens inhibited the response to the vaccine insert. Alternatively, the strong anamnestic response to a boost of protein antigens suggests that the level of protein expression by the vector was the limiting factor. In future studies, we will test whether vectors with better growth characteristics and stronger antigen expression levels can improve antibody titers, elicit neutralizing antibodies, and protect against a viral challenge.