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New potent vaccine adjuvants are desirable for increasing the efficacy of novel vaccine modalities such as DNA and peptides. We therefore tested if syngeneic erythrocytes could serve as delivery vectors for selected HIV peptides and compared the potency of these constructs to immunization with peptides in phosphate buffered saline or in incomplete Freunds adjuvant. Immunization of mice with peptides in a low dose (5 ng) coupled to erythrocytes induced a weak immune response in mice. These peptides alone (5 μg) gave no immune responses, while formulating the peptides (50 μg) in IFA induced strong homologous immunity as well as prominent cross reactivity to a related mutant epitope. Thus, vaccine delivery using syngeneic erythrocytes, although attractive for clinical use, might be of limited value due to the low amount of antigen that can be loaded per erythrocyte. Findings Peptide-based vaccines have been shown to be immunogenic in animal models, and well tolerated in man [1,2]. One major benefit of peptide-based immunogens is the ease with which the vaccine can be modulated in order to fit new variants of a variable microbe such as HIV [3]. One application of such a vaccine strategy would be to target viral mutants conferring escape from antiretroviral drugs. As certain known mutations within epitopes of the HIV proteins are associated with resistance to the drugs [4] those epitopes variants could be included in a peptidebased vaccine. However these kinds of vaccines may need to be adjuvanted in order to be used in humans. The strategy of using syngeneic erythrocytes as delivery vectors is attractive, since no external compounds are used. Further, red blood cells (RBCs) are naturally removed by macrophages from the bloodstream and thereby targeted to immune cells. In addition, no toxic side effects have been found in host tissue following RBC-antigen delivery [5]. HIV Tat protein coupled to red blood cells was shown to induce as potent immune response as protein formulated in Freund's adjuvant [6]. The RBC method also induced protective immunity in mice and cats lethally challenged with HSV-1 and FIV-M2, respectively [7,8]. The objective Published: 18 April 2007 Infectious Agents and Cancer 2007, 2:9 doi:10.1186/1750-9378-2-9 Received: 8 December 2006 Accepted: 18 April 2007 This article is available from: http://www.infectagentscancer.com/content/2/1/9 © 2007 Boberg et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.