Comparison of the size distributions and immunogenicity of human papillomavirus type 16 L1 virus-like particles produced in insect and yeast cells

Abstract

Insect and yeast cells are considered the expression systems of choice for producing virus-like particles (VLPs), and numerous types of VLPs have been produced in these systems. However, previous studies were restricted to identifying the characteristics of individual VLP preparations. No direct comparison of the structures and immunogenic properties of insect and yeast-derived VLPs has so far been made. In the present study, the size distribution and immunogenic properties of human papillomavirus type 16 (HPV16) L1 VLPs produced in Spodoptera frugipedra-9 insect cells and Saccharomyces cerevisiae were compared. The insect cell-derived VLPs were larger than the yeast ones (P < 0.0001), with median sizes of 34 and 26 nm, respectively. In addition, the insect-derived VLPs appeared to be more diverse in size than the yeast-derived VLPs. Immunization of mice with 30 ng per dose of VLPs elicited 2.7- and 2.4-fold higher anti-HPV16 L1 IgG and anti-HPV16 neutralizing antibody titers than immunization with the same amounts of the yeast-derived VLPs after the 4th immunizations, respectively. Our results suggest that the choice of expression system critically affects the particle size and immunogenic property of HPV16 L1 VLPs.

A novel C-terminal modification method enhanced the yield of human papillomavirus L1 or chimeric L1-L2 virus-like particles in the baculovirus system

“…Their different immunogenicity and efficacy may be attributed to the different expression systems. Consistent with our speculation, a study in mice showed that HPV16 L1 VLPs produced in insect cells induced much higher neutralizing antibody titers than those produced in yeast in the absence of adjuvant (Kim et al, 2018). These data suggested that insect cells, a higher eukaryotic expression system, may be more conducive to generating highly immunogenic VLPs.…”

Methylparaben as a preservative in the development of a multi-dose HPV-2 vaccine

“…The particle size and distribution of VLPs are correlated with their immunogenicity. The closer to the real virus particle (<100 nm), the more symmetrical the VLP icosahedron and the stronger its immunogenicity, 21 as confirmed by our clinical phase III research results (results are not shown). Therefore, according to the change of particle size, at least 0.25% PH, 0.5% PH, 0.1% PE, 0.5% PE, 0.15% CR, 0.5% BA, 1.0% BA, 0.10% MP, and 0.14% MP can be used as preservatives for the HPV-2 vaccine.…”

Self-assembly into virus–like particles of the recombinant capsid protein of porcine circovirus type 3 and its application on antibodies detection

“…Previous studies have shown that expressing the full-length PCV3 cap gene and NLS domains presenting within the N-terminal arginine rich motif (ARM) may cause misfolding of the protein and induce formation of circular virus complexes of 10-12 nm (Sarker et al 2016). Other groups have published that, different sizes of VLPs appear in different expression systems (Bucarey et al 2009;Kim et al 2018a;Wu et al 2016), a number of factors including storage conditions (ion-strength, pH and etc.) as well as the process design also influence the characteristics of VLPs (Effio and Hubbuch 2015;Fernandes et al 2013;Kim and Kim 2017b).…”