The immunogenicity and efficacy of intranasally or parenterally administered replication-deficient vaccinia-parainfluenza virus type 3 recombinants in rhesus monkeys

Abstract

Immunization of rhesus monkeys with modified vaccinia Ankara (MVA) recombinants expressing the heamagglutinin-neuraminidase (HN) or fusion (F) glycoproteins of human parainfluenza virus type 3 (HPIV3) was compared with an intranasally-administered live, attenuated HPIV3 vaccine candidate, the cp45 derivative of the JS strain of wildtype HPIV3. The MVA recombinants, when given parenterally (i.m.) or as a parenteral-local (i.m. and i.t.) combination, induced an antibody response comparable to that of cp45 and protected the upper and lower respiratory tracts of the rhesus monkeys against challenge with wildtype HPIV3. When given by the i.n. route alone, the MVA PIV3 recombinants induced a serum antibody response that was comparable to that of cp45 and induced resistance in the lower respiratory tract. Despite the ability of the intranasally-administered MVA PIV3 recombinants to stimulate a good serological response and to protect the lower respiratory tract, they unexpectedly failed to induce a significant level of resistance in the upper respiratory tract. The live, attenuated virus vaccine candidate induced almost complete resistance in both the upper and lower tracts. The data thus identify two vaccine candidates that can protect both the upper and lower respiratory tracts of rhesus monkey, parenterally-administered MVA PIV3 and intranasally-administered cp45. Further studies with these vaccines in non-human primates and humans should identify the relative merits of these immunogens for use in the very young infant.