Simian Immunodeficiency Virus SIVmac239Δnef Vaccination Elicits Different Tat _28-35 SL8-Specific CD8 ⁺ T-Cell Clonotypes Compared to a DNA Prime/Adenovirus Type 5 Boost Regimen in Rhesus Macaques

Abstract

Different human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccine vectors ex-

Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection

“…Tissues from secondary lymphoid tissues, including lymph nodes and the spleen; the gut mucosa, including the jejunum, the ileum and the colon; and the female reproductive tract, including the cervix and the vagina, were processed and stained for CM9-MHC tetramer + and SL8-MHC tetramer + CD8 T cells. CM9 is a highly conserved epitope within the Gag protein, while Tat SL8 is a highly variable epitope that escapes CD8 T cell responses mounted against it frequently and rapidly [20, 26]. These two epitopes on opposite extremes of the immune evasion spectrum were chosen to determine if epitope entropy, a measure of an epitope’s mutational flexibility, plays a role in the maintenance of its CD8 T cell response in the tissues.…”

“…By week 20 after SIVΔnef vaccination, almost all CM9- and SL8-specific CD8 T cells in the jejunum, the colon, the ileum and the vagina upregulated CD69, in contrast to CD8 T cell responses in secondary lymphoid tissues and peripheral blood which were largely CD69- (Fig 11). Importantly, CD69 upregulation was not dependent on antigenic exposure, as the SL8 epitope is generally entirely escaped by week 5 [20, 26] nor was it a sign of CD8 T cell proliferation, as SIV-specific CD8 T cells in vaginal tissue demonstrated low Ki-67 expression at weeks 5 and 20 (Fig 10E, S5 Fig). Although SL8-specific CD8 T cells in gut and vaginal tissues also upregulated CD69 expression, the overall magnitude of the SL8 response dropped significantly in these tissues between weeks 5 and 20 (Fig 8C).…”

Adoptive Transfer of Lymphocytes Isolated from Simian Immunodeficiency Virus SIVmac239Δnef-Vaccinated Macaques Does Not Affect Acute-Phase Viral Loads but May Reduce Chronic-Phase Viral Loads in Major Histocompatibility Complex-Matched Recipients

“…Furthermore, because SIVmac239⌬nef replicated for 20 to 24 weeks in the donor macaques, it was possible that recipient animals were infected with virus that contained escape mutations in CD8 T cell epitopes shared between SIVmac239 and SIVmac239⌬nef (33). We previously reported five CD8 T cell epitopes restricted by MHC class I alleles shared by all animals in this cohort that accumulate mutations under CD8 T cell selection pressure (34,35).…”

DNA Vaccines for the Induction of Immune Responses in Mucosal Tissues

“…Recombinant virus vectors, often DNA viruses, are based on replication-defective adenoviruses confirmed to be safe, live, oral vaccines against adenoviral respiratory disease in military recruits, including types 4 and 7 (Hung et al, 1990). Type 5 adenovirus (rAd5) (Yoshimura et al, 1993) is currently used in several HIV-1 (Burwitz et al, 2011;Koblin et al, 2011;Schooley et al, 2010), influenza (Toro et al, 2011;Vemula and Mittal, 2010), hepatitis C (Desjardins et al, 2009), and other vaccines. Other frequently used viral vectors are derived from poxviruses, including vaccinia derivatives NYVAC (New York Vaccinia Virus), MVA (Modified Vaccinia Virus Ankara), and canarypox-based ALVAC (Panicali and Paoletti, 1982;Paoletti, 1996;Tartaglia et al, 1992), which have been tested in several HIV-1 (Aboud et al, 2010;Goepfert et al, 2011;Gorse et al, 2012;Gudmundsdotter et al, 2009;Hanke et al, 1999;Hansen et al, 1992;Hel et al, 2002;Lai et al, 2011;Liu et al, 2012;Moise et al, 2011;Perreau et al, 2011;Ramanathan et al, 2009;Richmond et al, 1997;Winstone et al, 2009), influenza (Breathnach et al, 2004;Degano et al, 1999;Smith et al, 1983), and hepatitis C (Deng et al, 2009) models among others.…”