Adjuvant-enhanced antibody responses to recombinant proteins correlates with protection of mice and monkeys to orthopoxvirus challenges

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• 作者：Christiana N. Fogg ; Jeffrey L. Americo ; Shlomo Lustig ; John W. Huggins ; Scott K. Smith ; Inger Damon ; Wolfgang Resch ; Patricia L. Earl ; Dennis M. Klinman ; Bernard Moss
• 关键词：Smallpox ; Monkeypox ; Vaccinia virus
• 刊名：Vaccine
• 出版年：2007
• 出版时间：12 April 2007
• 年：2007
• 卷：25
• 期：15
• 页码：2787-2799
• 全文大小：990 K

文摘

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.