Inducing dose sparing with inactivated polio virus formulated in adjuvant CAF01.

Jes Dietrich,Else Marie Agger,Peter Andersen,Lars Vibe Andreasen,Mauricio Martins Rodrigues

doi:10.1371/journal.pone.0100879

Abstract

The development of new low cost inactivated polio virus based vaccines (IPV) is a high priority, and will be required to eradicate polio. In addition, such a vaccine constitutes the only realistic polio vaccine in the post-eradication era. One way to reduce the cost of a vaccine is to increase immunogenicity by use of adjuvants. The CAF01 adjuvant has previously been shown to be a safe and potent adjuvant with several antigens, and here we show that in mice IPV formulated with CAF01 induced increased systemic protective immunity measured by binding and neutralization antibody titers in serum. CAF01 also influenced the kinetics of both the cellular and humoral response against IPV to produce a faster, as well as a stronger, response, dominated by IgG2a, IgG2b, and IgG2c isotypes as well as IPV specific T cells secreting IFN-γ/IL-2. Finally, as intestinal immunity is also a priority of polio vaccines, we present a vaccine strategy based on simultaneous priming at an intradermal and an intramuscular site that generate intestinal immune responses against polio virus. Taken together, the IPV-CAF01 formulation constitutes a new promising vaccine against polio with the ability to generate strong humoral and cellular immunity against the polio virus.

Highlights

Poliomyelitis is caused by the polio virus, an RNA virus that can colonize the gastroenteral tract which may lead to an acute, viral, infectious disease that spreads from person to person, primarily via the fecal-oral route
The Zavg of 35 nm is in accordance with values for polio virus size determined by electron microscopy (30 nm) indicating that the size did not change upon mixing of three Inactivated polio Vaccine (IPV) monovalents into a trivalent IPV (Fig. 1A)
The analysis of IPV content measured as D-unit activity confirmed that IPV D-unit activity was maintained after mixing of IPV1-3 into IPV TP (Fig. 1B)

Summary

Introduction

Poliomyelitis is caused by the polio virus, an RNA virus that can colonize the gastroenteral tract which may lead to an acute, viral, infectious disease that spreads from person to person, primarily via the fecal-oral route. Two vaccines exist against polio; Inactivated polio Vaccine (IPV) and Trivalent live Oral polio Virus (tOPV). TOPV with attenuated Sabin strains of poliovirus types 1, 2 and 3, has been the vaccine of choice for polio vaccination in most countries because it induces both systemic and intestinal immunity, can immunize or boost immunity of close contacts through secondary spread, and is inexpensive and easy to administer. Steps have been taken to discontinue OPV as a vaccine against polio, rendering IPV the only realistic polio vaccine in the post-eradication era

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