The present invention relates to therapeutic and prophylactic methods for treating or preventing an infectious disease in a subject by stimulating or enhancing an immune response against an infectious agent causing the disease. The methods comprise administering to the subject a plurality of compositions, each composition being administered to a different site of the subject, wherein each site is, or substantially drains to, an anatomically distinct lymph node, a group of lymph nodes, a nonencapsulated cluster of lymphoid tissue, or the spleen. Each composition comprises at least one antigenic molecule having one or more epitopes of the same infectious agent or a strain thereof. The antigenic molecules of each composition comprise in aggregate a set of epitopes distinct from that of any other composition that is administered to the subject.