Increased human immunodeficiency virus type 1 Env expression and antibody induction using an enhanced alphavirus vector.
Viral vectors encoding heterologous vaccine antigens are potent inducers of cellular immune responses, but they are generally less efficient at stimulating humoral immunity. To improve the induction of antibody responses by Semliki Forest virus-based vaccines, a vector encoding a translation-enhancer element and a novel internal signal sequence for increased expression and secretion of soluble antigens was designed. Approximately tenfold more human immunodeficiency virus type 1 gp120 was secreted into culture supernatants of infected cells using the enhanced vector compared with the parental vector. This translated into a significant increase in gp120-specific antibodies in immunized mice, suggesting that antigen-expression levels from the parental vector are limiting for induction of antibody responses. These data encourage the use of the enhanced vector for elicitation of immune responses against heterologous antigens during vaccination.
Forsell
Mattias N E
MNE
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden, and Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
McInerney
Gerald M
GM
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden, and Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
Dosenovic
Pia
P
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden, and Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
Hidmark
Åsa S
ÅS
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden, and Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
Eriksson
Christopher
C
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden, and Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
Liljeström
Peter
P
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden, and Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
Grundner
Christoph
C
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden, and Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
Karlsson Hedestam
Gunilla B
GB
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden, and Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D007668:Kidney; D008715:Methionine / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry; D012672:Semliki forest virus / Q000235:genetics* / Q000276:immunology; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics*
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; D008715:Methionine