2013 Annual Report
1a.Objectives (from AD-416):
This collaborative research project seeks to develop novel approaches to induce mucosal immune responses to Foot-and-Mouth Disease Virus (FMDV) vaccines. Specifically, we will evaluate the efficacy of mucosal adjuvants, delivered via the replication-defective human adenovirus 5 (hAd5) vector system along with the hAd5-FMD vaccine, for augmenting immunity and protection following mucosal or parenteral administration, to mice and swine.
1b.Approach (from AD-416):
The evaluation of mucosal adjuvants efficacy delivered through the Ad5 platform, to induce mucosal immune responses to FMDV will be conducted alone or in combination with FMDV vaccine for induction of protection in swine. Challenge studies will be performed utilizing homotypic virus. Approaches to increase the efficacy of mucosally delivered Ad5-vectored mucosal adjuvants will be evaluated.
The current approach to administering Foot-and-Mouth Disease Virus (FMDV) vaccines, including the replication defective human Ad5-FMDV vaccines, is that they are not administered to mucosal surfaces and in general induce little or no mucosal immunity. We have addressed this problem by designing an Ad5-vectored mucosal adjuvant (LTR-72) and co-administered the adjuvant with the Ad5-FMDV vaccine via the intranasal (IN) route or combined intranasal/intramuscular (IM) routes. Our goal is to achieve a high level of parenteral immunity in combination with substantial mucosal immunity, raising the probably of inducing sterilizing immunity by protecting the mucosal epithelium, the site of initial infection and virus replication.
Conducted proof-of-principle experiments that were performed in mice which showed very promising results. We also began testing a similar approach in pigs, with somewhat less promising results. We believe that part of the reason the mucosal/parenteral vaccine approach was less successful in pigs was due to an overwhelming challenge dose, so these studies may need to be repeated.
The most significant accomplishment over the life of this research project to date are the results which showed that although all six groups of vaccinated swine developed clinical signs after FMDV challenge, the two groups receiving the Ad5-A24 vaccine, with or without the LTR-72 adjuvant administered first IN, followed by an IM boost, were the most protected.
No technologies have been transferred to date. Publications for this reporting period include:
Alejo DM, Moraes MP, Liao X, Dias CC, Tulman ER, Diaz-San Segundo F, Rood D, Grubman MJ, Silbart LK. An adenovirus vectored mucosal adjuvant augments protection of mice immunized intranasally with an adenovirus-vectored foot-and-mouth disease virus subunit vaccine. Vaccine. 2013 Apr 26;31(18):2302-9. doi: 10.1016/j.vaccine.2013.02.060. Epub 2013 Mar 13. PubMed PMID: 23499593.