Many promising microbicide candidates are proteins or peptides, including neutralizing monoclonal antibodies (mAbs). Here, the expression of the HIV-neutralizing mAb b12 in transgenic plants is described. The plant-derived mAb b12 was shown to have gp120 binding activity and HIV-neutralizing activity in vitro. However, it is likely that a protein-based microbicide will need to comprise a combination of two or more products, in order to provide long-lasting and cross-clade protection. Building on the expression of mAb b12 and to address the need for a combinational agent, the expression of a fusion protein of mAb b12 with cyanovirin-N, another protein microbicide, has been explored. This fusion protein molecule is predicted to have four binding sites for HIV gp120 with two different specificities. The fusion protein was assembled and expressed in planta, and functionality was confirmed by gp120 binding and HIV neutralization in vitro. Each moiety of the fusion protein retained its binding ability to gp120. In addition, this fusion protein demonstrated increased anti-HIV potency compared to b12 or CV-N alone. This fusion protein addresses the requirement to combine microbicide products, and the production in plants is a step toward resolving the issues of manufacturing scalability and cost for developing countries.