Recent developments with live-attenuated recombinant paramyxovirus vaccines.

There is no vaccine currently approved for paramyxovirus-induced respiratory diseases in humans, despite their major clinical importance. We review the development and evaluation of new vaccine strategies based on live-attenuated chimeric and recombinant vaccines against human respiratory syncytial virus, human metapneumovirus and human parainfluenza viruses types 1 to 3, which are significant causes of upper and lower tract respiratory diseases. Most promising strategies are based on virus attenuation through (i) mutations in key genes involved in replication; (ii) deletion of accessory genes; or (iii) the use of a corresponding animal viral vector, such as bovine parainfluenza type 3 and Sendai virus, as a background for the expression of a viral glycoprotein. Indeed, the fusion (F), or attachment (HN/H/G) glycoproteins are the most immunogenic antigens in paramyxoviruses. For each strategy, we will review the immunogenicity (increase in neutralising antibody titres) and the protection conferred by the most promising recombinant vectored vaccines and list ongoing clinical trials. We will conclude by discussing the most important challenges regarding the introduction of such vaccines into immunisation programmes.