Adjuvant-enhanced antibody responses to recombinant proteins correlates with protection of mice and monkeys to orthopoxvirus challenges.
Recombinant proteins are being evaluated as smallpox and monkeypox vaccines because of their perceived safety compared to live vaccinia virus. Previously, we demonstrated that three or more injections of a Ribi-type adjuvant with a combination of three proteins from the outer membranes of intracellular (L1 protein) and extracellular (A33 and B5 proteins) forms of vaccinia virus protected mice against a lethal intranasal challenge with vaccinia virus. Here, we compared several adjuvants and found that QS-21 and to a lesser extent alum+CpG oligodeoxynucleotides accelerated and enhanced neutralizing antibody responses to a mixture of L1 and A33 proteins, provided the highest ratio of IgG2a to IgG1 isotype response, and protected mice against disease and death after only two immunizations 3 weeks apart. In addition, monkeys immunized with recombinant vaccinia virus proteins and QS-21 developed neutralizing antibody to monkeypox virus and had reduced virus load, skin lesions, and morbidity compared to the non-immunized group following monkeypox virus challenge.
Fogg
Christiana N
CN
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Americo
Jeffrey L
JL
Lustig
Shlomo
S
Huggins
John W
JW
Smith
Scott K
SK
Damon
Inger
I
Resch
Wolfgang
W
Earl
Patricia L
PL
Klinman
Dennis M
DM
Moss
Bernard
B
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D008807:Mice, Inbred BALB C; D008993:Monkeypox virus / Q000276:immunology; D009841:Oligonucleotides / Q000276:immunology / Q000494:pharmacology*; D018155:Orthopoxvirus / Q000276:immunology*; D011213:Poxviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D012503:Saponins / Q000276:immunology / Q000494:pharmacology*; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control; D014616:Vaccinia virus / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D009841:Oligonucleotides; D011994:Recombinant Proteins; D012503:Saponins; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C041524:aluminum sulfate; C078785:saponin QA-21V1