ABSTRACT
The genes encoding the measles virus (MV) haemagglutinin (H) and fusion (F) proteins were placed under the control of the human cytomegalovirus immediate early promoter in a replication-deficient adenovirus vector. Immunofluorescence and radioimmune precipitation demonstrated the synthesis of each protein and biological activity was confirmed by the detection of haemadsorption and fusion activities in infected cells. Oral as well as parenteral administration of the H-expressing recombinant adenovirus elicited a significant protective response in mice challenged with MV. While the F-expressing adenovirus failed to protect mice, cotton rats immunized with either the H- or F-expressing recombinant showed reduced MV replication in the lungs. Antibodies elicited in mice following immunization with either recombinant had no in vitro neutralizing activity, suggesting a protective mechanism involving a cell-mediated immune response. This study demonstrates the feasibility of using oral administration of adenovirus recombinants to induce protective responses to heterologous proteins.
Subject(s)
Adenoviridae , Defective Viruses , Hemagglutinins, Viral/immunology , Measles Vaccine/immunology , Measles/prevention & control , Viral Fusion Proteins/immunology , Adenoviridae/physiology , Administration, Oral , Animals , Antibodies, Viral/immunology , Cell Line , Cell Line, Transformed , Defective Viruses/physiology , Female , Genetic Vectors , Hemagglutinins, Viral/genetics , Humans , Injections, Intraperitoneal , Measles virus/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Rats , Sigmodontinae , Viral Fusion Proteins/genetics , Virus ReplicationABSTRACT
The measles virus (MV) nucleocapsid (N) protein gene has been inserted into a plasmid vector so as to place the gene under the control of the strong constitutive human cytomegalovirus major immediate early promoter. On intramuscular injection of pMV64 DNA into C3H/He mice, seroconversion with increasing titers of N-specific serum IgG antibodies was observed over a period of 3 months. However, when 3-week-old mice were immunized by intramuscular injection of pMV64 in a two-dose schedule, and challenged intracranially with a rodent-adapted measles virus strain (CAM/RB) at 5 weeks of age, no significant protective response was seen. The lack of effective protection evoked by DNA immunization in this model, where MV challenge must take place before 8 weeks of age, may be due to inefficient induction of cell-mediated immunity resulting from expression in muscle tissue, compounded by a relatively slow rise in immune response compared with that seen with the recombinant adenovirus.
