The recombinant globular head domain of the measles virus hemagglutinin protein as a subunit vaccine against measles

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• 作者：Liubov M. Lobanova^a ; ¹ ; Nelson F. Eng^a ; ² ; Malathy Satkunarajah^b ; ^c ; George K. Mutwiri^a ; ^d ; James M. Rini^b ; ^c ; Alexander N. Zakhartchouk^a ; ^{alex.zak@usask.ca}
• 关键词：Measles ; Adjuvants ; Virus neutralization ; Subunit vaccine
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：26 April, 2012
• 卷：30
• 期：20
• 页码：3061-3067
• 文件大小：433 K

摘要

Despite the availability of live attenuated measles virus (MV) vaccines, a large number of measles-associated deaths occur among infants in developing countries. The development of a measles subunit vaccine may circumvent the limitations associated with the current live attenuated vaccines and eventually contribute to global measles eradication. Therefore, the goal of this study was to test the feasibility of producing the recombinant globular head domain of the MV hemagglutinin (H) protein by stably transfected human cells and to examine the ability of this recombinant protein to elicit MV-specific immune responses. The recombinant protein was purified from the culture supernatant of stably transfected HEK293T cells secreting a tagged version of the protein. Two subcutaneous immunizations with the purified recombinant protein alone resulted in the production of MV-specific serum IgG and neutralizing antibodies in mice. Formulation of the protein with adjuvants (polyphosphazene or alum) further enhanced the humoral immune response and in addition resulted in the induction of cell-mediated immunity as measured by the production of MV H-specific interferon gamma (IFN-纬) and interleukin 5 (IL-5) by in vitro re-stimulated splenocytes. Furthermore, the inclusion of polyphosphazene into the vaccine formulation induced a mixed Th1/Th2-type immune response. In addition, the purified recombinant protein retained its immunogenicity even after storage at 37 掳C for 2 weeks.