Immunogenicity of mucosally-administered modified vaccinia Ankara expressing HIV-1 Env protein gp120 in rabbits (VAC8P.1047)

Abstract

Abstract Modified vaccinia Ankara (MVA) used as a vaccine vector expressing heterologous antigens has been demonstrated to be immunogenic when delivered parenterally while its immunogenicity after mucosal delivery is less defined. To determine the immunogenicity of MVA when administered via different mucosal routes, NZW rabbits were vaccinated on day 0 and 28 with 3 x 108 PFU MVA expressing HIV-1 gp120 by nasal, rectal, or gastric routes. Intramuscular immunization with 1 x 108 PFU of the MVA vaccine was used as the positive control. Serum was collected on days 21 and 42 and antigen-specific antibodies were determined by ELISA. While intramuscular vaccination was the only route that induced a significantly elevated anti-gp120 serum IgG titer, nasal vaccination induced detectable anti-gp120 IgG response on day 42. Immunization by rectal or gastric routes did not induce measurable anti-gp120 IgG responses. Intramuscular and intranasal vaccination, but not gastric or rectal vaccination with MVA, induced significantly elevated serum IgG responses to pox proteins A33R and B5R. We conclude that, under the conditions tested, MVA vaccine vectors are immunogenic when delivered intramuscularly and intranasally but not gastrically or rectally. Insert specific responses after nasal vaccination were not comparable to those achieved by intramuscular vaccination, indicating that use of MVA as a nasal vaccine vector will need to be optimized.