The present invention relates to the design of gene transfer vectors and especially provides lentiviral gene transfer vectors suitable for either a unique administration or, for iterative administration in a host, and to their medicinal application (such as vaccination against Immunodeficiency Virus, especially suitable in human hosts). Gene transfer vectors are either integrative or non-integrative (NI) vectors, dependently upon the purpose of their use. The invention relates to the use of gene transfer vectors for unique or for multiple in vivo administration into a host in need thereof. The field of application of the present application concerns in particular animal treatment or treatment of human being (e.g. prophylactic or therapeutic or symptomatic or curative treatment), gene therapy or vaccination in vivo. These vectors may be used to elicit an immune response to prevent or to treat a pathogenic state, including virus infections (for example treatment or prevention against Immunodeficiency Virus and especially against AIDS), parasite and bacterial infections or cancers, and preferably to elicit a protective, long-lasting immune response.