Safety and Immunogenicity of a Replication‐Incompetent Adenovirus Type 5 HIV‐1 Clade Bgag/pol/nefVaccine in Healthy Adults

Abstract

The vaccine was generally well tolerated and induced cell-mediated immune responses against human immunodeficiency virus type 1 peptides in most healthy adults. Despite these findings, vaccination in a proof-of-concept trial with use of this vaccine was discontinued because of lack of efficacy.

Vaccines Expressing the Innate Immune Modulator EAT-2 Elicit Potent Effector Memory T Lymphocyte Responses despite Pre-Existing Vaccine Immunity

“…Recombinant adenovirus serotype 5 (rAd5)-based vaccines expressing several HIV-1 Ags have been shown to induce HIV-1-specific humoral, as well as potent cellular, immune responses in human trials (11,12). However, pre-existing immunity against Ad5 is present in 50-90% of normal human adults (13).…”

“…However, pre-existing immunity against Ad5 is present in 50-90% of normal human adults (13). In vaccines given HIV-1-targeted Ad vaccines, the presence of preexisting anti-Ad5 humoral and cellular immunity may have limited the overall efficacy of Ad5 HIV-1 vaccines in trial participants (11,12,14). Several approaches have therefore been developed to circumvent pre-existing anti-Ad5 immunity and/or to facilitate the induction of potent adaptive immune responses by Ad-based vaccines in general.…”

Molecular vaccines for malaria

“…[165][166][167][168] Reports addressing the impact of pre-existing Ad5 neutralizing antibody on adenovector vaccine immunogenicity in the clinic (with HIV vaccines) indicated that volunteers possessing high titers of Ad5 neutralizing antibody were capable of mounting significant antigen-specific humoral and cellular responses. 150,169,170 However, the magnitude of the T cell responses in individuals with pre-existing Ad5 NAb was approximately three-fold lower than those of the Ad5-seronegative volunteers.…”

Transient IL-10 receptor blockade can enhance CD8+T cell responses to a simian adenovirus-vectored HIV-1 conserved region immunogen

“…1 Replication-deficient adenoviruses are attractive vectors for HIV-1 immunogen delivery due to their excellent safety profile and capacity to induce potent immune responses. 2 However, development of human adenovirus 5 (HAdV5) vectored HIV-1 vaccines has ceased due to poor immunogenicity and disappointing clinical trial results, 3,4 as well as concerns regarding an association between pre-existing humoral immunity to HAdV5 and increased HIV-1 acquisition. 3 The field has now turned to rare human adenoviruses (HAdVs 26 and 35) and simian adenovirus ChAdV63 for which seroprevalence in humans is low.…”