Single oral immunization with replication deficient recombinant adenovirus elicits long-lived transgene-specific cellular and humoral immune responses.

Abstract:

:Oral-gastric delivery of vaccines is a preferred route of immunization and is particularly relevant to the development of vaccine-vector systems. We have investigated the ability of a replication deficient (E1-deleted) adenovirus construct (RAd68), which efficiently expresses the measles virus nucleocapsid (N) protein under the control of the strong HCMV IE promoter, to elicit antibody and cytotoxic T cell (CTL) responses in mice following intragastric administration. Measles virus N protein-specific CTL memory and serum antibody responses were analyzed in a total of 140 mice at time points 2-51 weeks after immunization either with a single dose of 10(8) pfu RAd68 or with a fivefold higher dose. Of the 20 animals analyzed in the first 4-week period following low-dose immunization, 6 mounted low-level splenic CTL responses while 13 animals had CTL in the mesenteric lymph nodes. Splenic CTL responses were largely undetectable at later times. Only 23% of low-dose-immunized mice made serum antibody responses and these were generally of low magnitude and frequently of short duration. In contrast, the majority of animals immunized orally with 5 x 10(8) pfu RAd68 mounted splenic CTL responses (70%) and/or antibody responses (89%). Notably, these responses were stronger and of greater duration than those seen following immunization at the lower dose. Gut mucosal immunization with replication deficient adenoviruses is a promising approach, not only for the development of complementary measles vaccine strategies which may be required for measles virus eradication, but also generally for vaccination against other infections.

journal_name

Virology

journal_title

Virology

authors

Sharpe S,Fooks A,Lee J,Hayes K,Clegg C,Cranage M

doi

10.1006/viro.2001.1281

subject

Has Abstract

pub_date

2002-02-15 00:00:00

pages

210-6

issue

2

eissn

0042-6822

issn

1096-0341

pii

S0042682201912814

journal_volume

293

pub_type

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