This document provides methods and materials related to polypeptides present in a vaccinia virus (e.g., membrane proteins such as vaccinia virus B5R, L1R, A33R, or A27L polypeptides). For example, methods for generating a vaccine comprising one or more of vaccinia virus polypeptides disclosed herein for preventing or treating Orthopoxvirus infection are provided. In addition, kits related to the use of vaccinia polypeptides are provided.
