Peptide Nanoparticles as Novel Immunogens: Design and Analysis of a Prototypic Severe Acute Respiratory Syndrome Vaccine

Abstract

Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel coronavirus that cost nearly 800 lives. While there have been no recent outbreaks of the disease, the threat remains as SARS coronavirus (SARS-CoV) like strains still exist in animal reservoirs. Therefore, the development of a vaccine against SARS is in grave need. Here, we have designed and produced a prototypic SARS vaccine: a self-assembling polypeptide nanoparticle that repetitively displays a SARS B-cell epitope from the C-terminal heptad repeat of the virus’ spike protein. Biophysical analyses with circular dichroism, transmission electron microscopy and dynamic light scattering confirmed the computational design showing α-helcial nanoparticles with sizes of about 25 nm. Immunization experiments with no adjuvants were performed with BALB/c mice. An investigation of the binding properties of the elicited antibodies showed that they were highly conformation specific for the coiled-coil epitope because they specifically recognized the native trimeric conformation of C-terminal heptad repeat region. Consequently, the antisera exhibited neutralization activity in an in vitro infection inhibition assay. We conclude that these peptide nanoparticles represent a promising platform for vaccine design, in particular for diseases that are characterized by neutralizing epitopes with coiled-coil conformation such as SARS-CoV or other enveloped viruses.

Expression of peptide nanoparticles containing a porcine reproductive and respiratory syndrome (PRRS) virus epitope in plants

“…As shown in Figure 1, we were able to obtain particles in both cases with sizes between 16-25 nm. The size and morphology of the nanoparticles closely resembled those obtained in bacteria (Babapoor et al, 2011;Kaba et al, 2009;Pimentel et al, 2009). This data demonstrated that nanoparticles were successfully Uribe-Campero et al 1603 formed in the plant cytoplasm.…”

“…When the sequence of these nanoparticles was expressed in E. coli and purified, no particles were obtained, they had to be subjected to several folding treatments in vitro for the particles to assemble (Raman et al, 2006;Pimentel et al 2009). However, in our case, the nanoparticles were able to self-assemble spontaneously in the plant cytoplasm without any further treatment.…”

“…These repetitive patterns are efficiently recognized by the mammal immune system. Epitopes that are capable of inducing an immune response can be displayed repetitively at high density on different types of nanoparticles (Pimentel et al, 2009). The key role of epitope density was illustrated in a study showing that nanoparticles decorated with a peptide at different density produce high IgG responses only at the highest density (Jegerlehner et al, 2002) and that only highly repetitive antigens could break B cell unresponsiveness and induce self-specific antibody responses (Bachmann et al, 1993;Chackerian et al, 2002).…”

“…A nanoparticle with this type of architecture can be used as a vaccine by extending the ends of the monomer with an epitope sequence (Babapoor et al, 2011). Nanoparticles of this type have only been expressed in bacterial systems and employed to express epitopes of Plasmodium berghei (Kaba et al, 2009), avian influenza (Babapoor et al, 2011) and severe acute respiratory syndrome virus (Pimentel et al, 2009).…”

pH-triggered peptide self-assembly into fibrils: a potential peptide-based subunit vaccine delivery platform

“…We have extensively used exogenous lipids and polymers to form self-adjuvanting delivery systems that obviate the use of toxic adjuvants [8][9][10][11][12][13]. Recently, it has been reported that self-assembled peptides exclusively composed of endogenous amino acids were able to stimulate immune responses [14][15][16].…”