Most commercialized virus-like particle (VLP) vaccines use
aluminum salt as adjuvant, even though VLPs provoke adequate
antibody responses without adjuvant. We do not have
detailed knowledge of how adjuvant affects the profile of anti-
VLP antibodies. Meanwhile, there is evidence that differences
between vaccination protocols influence the glycosylation of
antibodies, which may alter their effector functions. In the
present study a murine model was used to investigate the effects
of dosing schedule and adjuvant on the antibody profiles
and glycosylation levels of antigen-specific antibody responses
to human papillomavirus type 16 L1 (HPV16 L1)
VLPs. Mice received subcutaneously 2,000 ng of antigen divided
into 4 or 7 doses. The HPV16 L1 VLPs elicited > 4 log10
anti-HPV16 L1 IgG titers without adjuvant, and aluminum
hydroxide as adjuvant increased IgG titers 1.3- to 4-fold and
reduced the anti-HPV16 L1 IgG2a / anti-HPV16 L1 IgG1
ratio value (use of aluminum hydroxide reduced the ratio of
the IgG2a). Immunization with HPV16 L1 VLPs in combination
with Freund’s adjuvant enhanced IgG titers 5- to 12-
fold. Seven-dose immunization markedly increased anti-
HPV16 L1 IgM titers compared to four-dose immunization,
as well as increasing the proportion of glycosylated antibodies.
Our results suggest that antibody glycosylation can be controlled
immunologically, and IgG and IgM profiles and glycosylation
profiles of the vaccine-induced antibodies can be
used as indicators reflecting the vaccine characteristics. These results indicate that the HPV16 L1 VLP dosing schedule can
affect the quality of antigen-specific antibody responses. We
suggest that dosing schedules should be noted in vaccination
protocols for VLP-based vaccines.
Citations
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Emerging viruses pose a major threat to humans and livestock
with global public health and economic burdens. Vaccination
remains an effective tool to reduce this threat, and
yet, the conventional cell culture often fails to produce sufficient
vaccine dose. As an alternative to cell-culture based
vaccine, virus-like particles (VLPs) are considered as a highpriority
vaccine strategy against emerging viruses. VLPs represent
highly ordered repetitive structures via macromolecular
assemblies of viral proteins. The particulate nature allows efficient
uptake into antigen presenting cells stimulating both
innate and adaptive immune responses towards enhanced
vaccine efficacy. Increasing research activity and translation
opportunity necessitate the advances in the design of VLPs
and new bioprocessing modalities for efficient and cost-effective
production. Herein, we describe major achievements
and challenges in this endeavor, with respect to designing
strategies to harnessing the immunogenic potential, production
platforms, downstream processes, and some exemplary case s in developing VLP-based vaccines.
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