Pay more attention to the immunologically comparative evaluation of HIV-1 DNA vaccine in combination with adjuvant cytokines: a long way to go

Abstract

To the Editor: A recent article entitled “HIV-1 DNA vaccine with adjuvant cytokines induces specific immune responses against HIV-1 infection in mice” was published in the Chinese Medical Journal.1 The authors descriptively analyzed the adjuvant potential of an interleukin-12 (IL-12), interleukin-18 (IL-18), regulated on activation of normal T-cell expressed and secreted factor (RANTES), macrophage inflammatory protein 1 alpha (MIP-1α) or stromal cell derived factor 1 (SDF-1) plasmid when coimmunized with an HIV Gag gene-based DNA vaccine. Consequently the authors believed that IL-12, IL-18, or SDF-1 plasmid DNA potentially serves as immune adjuvants in combination with therapeutic HIV-1 DNA vaccine. The RANTES, MIP-1α plasmid DNA potentially serves as immune adjuvants in combination with HIV-1 prophylactic vaccine. Although the experiment allows us to consider such a coinoculation strategy as one of the means against HIV-1 infection, some special attentions should be highlighted. First, the authors did not set a saline control group, while female BALB/c mice were grouped. If the control were added, the analysis might be more convincing. After all, the eukaryotic expression vector might have the ocogenic potential or other detrimental effects. Second, the authors stated that the Gag gene was cloned into the pCI-neo mammalian expression vector. Some foreign genes used were cloned into other different vectors such as pVAX1. However, it is not clear which vectors were used for RANTES, MIP-1α, and SDF-1, although the authors mentioned that these recombinant plasmids were generous gifts from other researcher. In fact, the author might have ignored the immune discrepancy caused by the expression efficacy of different vectors, which may result in the uncertainty of the conclusion. Evidently, to construct and compare the expression ability of different eukaryotic expression vectors is a ceaseless work in vaccinology and other related fields. Third, although the authors have employed ELISA to detect the antibody production and the level of IFN-γ as well as performed the lymphoproliferation assays, some more direct analyses including immunofluorescence and Western blot may be added in order to confirm the expression of the genes of interest. Alternatively, immunopathology is also a suitable complimentary to this kind of study. Fourth, the usage of the female BALB/c mice only as animal models for HIV study is not very optimal, compared with that of primates. If other animals could not be adopted because of the limitation of experimental condition, both male and female mice should be used to get a more objective evaluation. Last but not least, the whole immune system is a very complicated network. Although the published article did a contribution to the comparative evaluation of the immune efficacy of HIV-1 DNA vaccine with adjuvant cytokines against HIV-1 infection in mice, currently however, it is difficult to predict whether such a contribution can ultimately clear organism from HIV or induce effective immunoreaction regardless of whether some cytokines and other beneficial components are combined.2 HIV is posing a threat against our life and the current knowledge with respect to HIV is rather limited. Both humoral and cellular immune responses will be responsible for the elimination of HIV infection. To date studies on protective effect of DNA- mediated immunization with a combination of various adjuvants against infection of different pathogens have received extensive attentions both nationally and internationally.3–6 More endeavors are needed for elucidating the immunologic mechanisms of DNA direct injection, although no specialist in the field of immunology seemed able to agree with another.