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Abstract

Vaccination with live attenuated simian immunodeficiency virus (SIV) in non-human primate species provides a means of characterizing the protective processes of retroviral superinfection and may lead to novel advances of human immunodeficiency virus (HIV)/AIDS vaccine design. The minimally attenuated SIVmacC8 vaccine has been demonstrated to elicit early potent protection against pathogenic rechallenge with genetically diverse viral isolates in cynomolgus macaques (). In this study, we have characterized further the biological breadth of this vaccine protection by assessing the ability of both the -disrupted SIVmacC8 and its -intact counterpart SIVmacJ5 viruses to prevent superinfection with the macrophage/neurotropic SIVmac239/17E-Fr (SIVmac17E-Fr) isolate. Inoculation with either SIVmacC8 or SIVmacJ5 and subsequent detailed characterization of the viral replication kinetics revealed a wide range of virus–host outcomes. Both -disrupted and -intact immunizing viruses were able to prevent establishment of SIVmac17E-Fr in peripheral blood and secondary lymphoid tissues. Differences in virus kinetics, indicative of an active process, identified uncontrolled replication in one macaque which although able to prevent SIVmac17E-Fr superinfection led to extensive neuropathological complications. The ability to prevent a biologically heterologous, CD4-independent/CCR5 viral isolate and the macrophage-tropic SIVmac316 strain from establishing infection supports the hypothesis that direct target cell blocking is unlikely to be a central feature of live lentivirus vaccination. These data provide further evidence to demonstrate that inoculation of a live retroviral vaccine can deliver broad spectrum protection against both macrophage-tropic as well as lymphocytotropic viruses. These data add to our knowledge of live attenuated SIV vaccines but further highlight potential safety concerns of vaccinating with a live retrovirus.

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2015-07-01
2022-01-25
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References

  1. Almond N., Kent K., Cranage M., Rud E., Clarke B., Stott E.J. (1995). Protection by attenuated simian immunodeficiency virus in macaques against challenge with virus-infected cellsLancet 34513421344 [View Article][PubMed]. [Google Scholar]
  2. Almond N., Rose J., Sangster R., Silvera P., Stebbings R., Walker B., Stott E.J. (1997). Mechanisms of protection induced by attenuated simian immunodeficiency virus. I. Protection cannot be transferred with immune serumJ Gen Virol 7819191922[PubMed]. [Google Scholar]
  3. Berry N., Stebbings R., Ferguson D., Ham C., Alden J., Brown S., Jenkins A., Lines J., Duffy L., other authors. (2008). Resistance to superinfection by a vigorously replicating, uncloned stock of simian immunodeficiency virus (SIVmac251) stimulates replication of a live attenuated virus vaccine (SIVmacC8)J Gen Virol 8922402251 [View Article][PubMed]. [Google Scholar]
  4. Berry N., Ham C., Mee E.T., Rose N.J., Mattiuzzo G., Jenkins A., Page M., Elsley W., Robinson M., other authors. (2011). Early potent protection against heterologous SIVsmE660 challenge following live attenuated SIV vaccination in Mauritian cynomolgus macaquesPLoS One 6e23092 [View Article][PubMed]. [Google Scholar]
  5. Cantó-Nogués C., Jones S., Sangster R., Silvera P., Hull R., Cook R., Hall G., Walker B., Stott E.J., other authors. (2001). In situ hybridization and immunolabelling study of the early replication of simian immunodeficiency virus (SIVmacJ5) in vivo J Gen Virol 8222252234[PubMed]. [Google Scholar]
  6. Clarke S., Almond N., Berry N. (2003). Simian immunodeficiency virus Nef gene regulates the production of 2-LTR circles in vivoVirology 306100108 [View Article][PubMed]. [Google Scholar]
  7. Clarke S., Berry N., Ham C., Alden J., Almond N., Ferguson D. (2012). Neuropathology of wild-type and nef-attenuated T cell tropic simian immunodeficiency virus (SIVmac32H) and macrophage tropic neurovirulent SIVmac17E-Fr in cynomolgus macaquesJ Neurovirol 18100112 [View Article][PubMed]. [Google Scholar]
  8. Clements J.E., Babas T., Mankowski J.L., Suryanarayana K., Piatak M. Jr, Tarwater P.M., Lifson J.D., Zink M.C. (2002). The central nervous system as a reservoir for simian immunodeficiency virus (SIV): steady-state levels of SIV DNA in brain from acute through asymptomatic infectionJ Infect Dis 186905913 [View Article][PubMed]. [Google Scholar]
  9. Connor R.I., Montefiori D.C., Binley J.M., Moore J.P., Bonhoeffer S., Gettie A., Fenamore E.A., Sheridan K.E., Ho D.D., other authors. (1998). Temporal analyses of virus replication, immune responses, and efficacy in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccineJ Virol 7275017509[PubMed]. [Google Scholar]
  10. Daniel M.D., Kirchhoff F., Czajak S.C., Sehgal P.K., Desrosiers R.C. (1992). Protective effects of a live attenuated SIV vaccine with a deletion in the nef geneScience 25819381941 [View Article][PubMed]. [Google Scholar]
  11. Edinger A.L., Mankowski J.L., Doranz B.J., Margulies B.J., Lee B., Rucker J., Sharron M., Hoffman T.L., Berson J.F., other authors. (1997). CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strainProc Natl Acad Sci U S A 941474214747 [View Article][PubMed]. [Google Scholar]
  12. Ferguson D., Mattiuzzo G., Ham C., Stebbings R., Li B., Rose N.J., Mee E.T., Smith D., Page M., other authors. (2014). Early biodistribution and persistence of a protective live attenuated SIV vaccine elicits localised innate responses in multiple lymphoid tissuesPLoS One 9e104390 [View Article][PubMed]. [Google Scholar]
  13. Flaherty M.T., Hauer D.A., Mankowski J.L., Zink M.C., Clements J.E. (1997). Molecular and biological characterization of a neurovirulent molecular clone of simian immunodeficiency virusJ Virol 7157905798[PubMed]. [Google Scholar]
  14. Fukazawa Y., Park H., Cameron M.J., Lefebvre F., Lum R., Coombes N., Mahyari E., Hagen S.I., Bae J.Y., other authors. (2012). Lymph node T cell responses predict the efficacy of live attenuated SIV vaccinesNat Med 1816731681 [View Article][PubMed]. [Google Scholar]
  15. Johnson R.P., Lifson J.D., Czajak S.C., Cole K.S., Manson K.H., Glickman R., Yang J., Montefiori D.C., Montelaro R., other authors. (1999). Highly attenuated vaccine strains of simian immunodeficiency virus protect against vaginal challenge: inverse relationship of degree of protection with level of attenuationJ Virol 7349524961[PubMed]. [Google Scholar]
  16. Koff W.C., Johnson P.R., Watkins D.I., Burton D.R., Lifson J.D., Hasenkrug K.J., McDermott A.B., Schultz A., Zamb T.J., other authors. (2006). HIV vaccine design: insights from live attenuated SIV vaccinesNat Immunol 71923 [View Article][PubMed]. [Google Scholar]
  17. Li B., Berry N., Ham C., Ferguson D., Smith D., Hall J., Page M., Quartey-Papafio R., Elsley W., other authors. (2011). Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+T cellsRetrovirology 88 [View Article][PubMed]. [Google Scholar]
  18. Lifson J.D., Nowak M.A., Goldstein S., Rossio J.L., Kinter A., Vasquez G., Wiltrout T.A., Brown C., Schneider D., other authors. (1997). The extent of early viral replication is a critical determinant of the natural history of simian immunodeficiency virus infectionJ Virol 7195089514[PubMed]. [Google Scholar]
  19. Mankowski J.L., Flaherty M.T., Spelman J.P., Hauer D.A., Didier P.J., Amedee A.M., Murphey-Corb M., Kirstein L.M., Muñoz A., other authors. (1997). Pathogenesis of simian immunodeficiency virus encephalitis: viral determinants of neurovirulenceJ Virol 7160556060[PubMed]. [Google Scholar]
  20. Manoussaka M., Berry N., Ferguson D., Stebbings R., Robinson M., Ham C., Page M., Li B., Das A., other authors. (2013). Conditionally-live attenuated SIV upregulates global T effector memory cell frequency under replication permissive conditionsRetrovirology 1059 [View Article][PubMed]. [Google Scholar]
  21. Mansfield K., Lang S.M., Gauduin M.C., Sanford H.B., Lifson J.D., Johnson R.P., Desrosiers R.C. (2008). Vaccine protection by live, attenuated simian immunodeficiency virus in the absence of high-titer antibody responses and high-frequency cellular immune responses measurable in the peripheryJ Virol 8241354148 [View Article][PubMed]. [Google Scholar]
  22. Micci L., Alvarez X., Iriele R.I., Ortiz A.M., Ryan E.S., McGary C.S., Deleage C., McAtee B.B., He T., other authors. (2014). CD4 depletion in SIV-infected macaques results in macrophage and microglia infection with rapid turnover of infected cellsPLoS Pathog 10e1004467 [View Article][PubMed]. [Google Scholar]
  23. Mori K., Ringler D.J., Desrosiers R.C. (1993). Restricted replication of simian immunodeficiency virus strain 239 in macrophages is determined by env but is not due to restricted entryJ Virol 6728072814[PubMed]. [Google Scholar]
  24. Mori K., Rosenzweig M., Desrosiers R.C. (2000). Mechanisms for adaptation of simian immunodeficiency virus to replication in alveolar macrophagesJ Virol 741085210859 [View Article][PubMed]. [Google Scholar]
  25. Norley S., Beer B., Binninger-Schinzel D., Cosma C., Kurth R. (1996). Protection from pathogenic SIVmac challenge following short-term infection with a nef-deficient attenuated virusVirology 219195205 [View Article][PubMed]. [Google Scholar]
  26. Puffer B.A., Pöhlmann S., Edinger A.L., Carlin D., Sanchez M.D., Reitter J., Watry D.D., Fox H.S., Desrosiers R.C., Doms R.W. (2002). CD4 independence of simian immunodeficiency virus Envs is associated with macrophage tropism, neutralization sensitivity, and attenuated pathogenicityJ Virol 7625952605 [View Article][PubMed]. [Google Scholar]
  27. Rud E.W., Cranage M., Yon J., Quirk J., Ogilvie L., Cook N., Webster S., Dennis M., Clarke B.E. (1994). Molecular and biological characterization of simian immunodeficiency virus macaque strain 32H proviral clones containing nef size variantsJ Gen Virol 75529543 [View Article][PubMed]. [Google Scholar]
  28. Sharma D.P., Zink M.C., Anderson M., Adams R., Clements J.E., Joag S.V., Narayan O. (1992). Derivation of neurotropic simian immunodeficiency virus from exclusively lymphocytetropic parental virus: pathogenesis of infection in macaquesJ Virol 6635503556[PubMed]. [Google Scholar]
  29. Silvera P., Wade-Evans A., Rud E., Hull R., Silvera K., Sangster R., Almond N., Stott J. (2001). Mechanisms of protection induced by live attenuated simian immunodeficiency virus: III. Viral interference and the role of CD8+T-cells and beta-chemokines in the inhibition of virus infection of PBMCs in vitroJ Med Primatol 30113 [View Article][PubMed]. [Google Scholar]
  30. Staprans S.I., Dailey P.J., Rosenthal A., Horton C., Grant R.M., Lerche N., Feinberg M.B. (1999). Simian immunodeficiency virus disease course is predicted by the extent of virus replication during primary infectionJ Virol 7348294839[PubMed]. [Google Scholar]
  31. Stebbings R., Berry N., Stott J., Hull R., Walker B., Lines J., Elsley W., Brown S., Wade-Evans A., other authors. (2004). Vaccination with live attenuated simian immunodeficiency virus for 21 days protects against superinfectionVirology 330249260 [View Article][PubMed]. [Google Scholar]
  32. Stebbings R., Berry N., Waldmann H., Bird P., Hale G., Stott J., North D., Hull R., Hall J., other authors. (2005). CD8+ lymphocytes do not mediate protection against acute superinfection 20 days after vaccination with a live attenuated simian immunodeficiency virusJ Virol 791226412272 [View Article][PubMed]. [Google Scholar]
  33. UNAIDS (2013). Global Reporthttp://www.unaids.org/. [Google Scholar]
  34. Watson A., Ranchalis J., Travis B., McClure J., Sutton W., Johnson P.R., Hu S.L., Haigwood N.L. (1997). Plasma viremia in macaques infected with simian immunodeficiency virus: plasma viral load early in infection predicts survivalJ Virol 71284290[PubMed]. [Google Scholar]
  35. Williams K.C., Corey S., Westmoreland S.V., Pauley D., Knight H., deBakker C., Alvarez X., Lackner A.A. (2001). Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDSJ Exp Med 193905915 [View Article][PubMed]. [Google Scholar]
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