Subunit and Virus-Like Particle Vaccine Approaches for Respiratory Syncytial Virus

Abstract

Despite its impact on global health, there is no vaccine available for the prevention of respiratory syncytial virus (RSV) infection. Failure to develop a licensed vaccine is not due to lack of effort, as numerous vaccine candidates have been characterized in preclinical and clinical studies spanning five decades. The vaccine candidates thus far explored can be generally divided into four categories: (1) whole inactivated virus, (2) replication competent, attenuated virus including recombinant viruses, (3) gene-based vectors, and (4) subunit and particulate forms of RSV antigens. The first clinically tested RSV vaccine candidate was a formalin-inactivated purified virus preparation administered to infants and children in the late 1960s. Due to the disastrous outcome of these trials and results of animal models investigating the mechanisms involved, there have been no further studies with inactivated RSV vaccines. Rather, efforts have focused on development of other approaches. In this chapter, we review the history and status of purified proteins, peptides, virus-like particles, virosomes, and nanoparticles and discuss their future potential.

Influence of Respiratory Syncytial Virus F Glycoprotein Conformation on Induction of Protective Immune Responses

“…Although in most cases, induction of neutralizing antibodies and protection were achieved in mice or cotton rats (53,54), there were cases in which pathology was also noted, depending on the adjuvant and route of vaccination. Hence, postfusion F may have the drawback of priming for pathology, although this is probably not the case in individuals who have been previously infected with hRSV (8). Our results indicate that protective doses of prefusion F may be less pathogenic, but a more extensive safety profile needs to be investigated.…”

“…In addition, a Th2-biased CD4 T-cell response, characterized by the production of allergic inflammation, including interleukin-4 (IL-4) production, may also have contributed to the enhanced disease observed in the FI hRSV vaccine trial (6). However, disease enhancement is not observed with live attenuated hRSV strains (7) or with subunit vaccines in individuals who have experienced previous RSV infections (8).…”

The Pneumovirinae fusion (F) protein: A common target for vaccines and antivirals

“…However, it has been reported that immunization of rabbits with vaccinia virus recombinants expressing full-length hRSV F protein induces pre-fusion specific antibodies (Magro et al, 2012). Therefore, although it needs to be proven, it is likely that attenuated virus vaccines or live vaccine vectors (Morrison and Walsh, 2013) that have the capacity to express pre-fusion F protein at the cell surface will be also capable of inducing highly neutralizing pre-fusion specific antibodies. Alternatively, as already mentioned, engineered soluble forms of F, stabilized in the pre-fusion conformation may be efficient inducers of neutralizing antibodies and thus promising hRSV vaccine candidates (McLellan et al, 2013a).…”

Determinants of early life immune responses to RSV infection

“…A failed vaccine trial nearly 50 years ago has given the vaccinationof infants against RSVan unfortunate legacy, and many are wary of the potential to enhance disease in infant populations using protein-based or inactivated virus vaccines [39,40]. FI-RSVvaccine administered in the 1960s was an adaptation of an approach successfully usedforpreventing disease from pathogens such as polio, but in the case of RSV resulted in enhanced disease after natural infection and the deaths of two children [41].…”