Inactivated Whole SIV Vaccine in Macaques: Evaluation of Protective Efficacy Against Challenge with Cell-Free Virus or Infected Cells

Johnson, Philip R.; Montefiori, David C.; Goldstein, Simon; Hamm, Tiffany E.; Zhou, Ji; Kitov, Svetlana; Haigwood, Nancy L.; Misher, Lynda; London, William T.; Gerin, John L.; Allison, A. C.; Purcell, Robert H.; Chanock, Robert M.; Hirsch, Vanessa M.

doi:10.1089/aid.1992.8.1501

Cited by 23 publications

(7 citation statements)

References 11 publications

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“…Sera from multiparous women, polytransfused patients, and other alloimmunized individuals destroys HIV particles and inhibits HIV infection in vitro (108)(109)(110) and similar results have been observed in animal systems with other retroviruses (35,36,111). Also, vaccination studies have demonstrated that induced responses to host cell proteins present in retroviral particles can provide prophylactic resistance to retroviral infection (112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123).…”

Section: Evidence For the Antiretroviral Nature Of Alloimmunitysupporting

confidence: 54%

The Trojan exosome hypothesis

Gould

Booth

Hildreth³

2003

Proc. Natl. Acad. Sci. U.S.A.

563

486

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We propose that retroviruses exploit a cell-encoded pathway of intercellular vesicle traffic, exosome exchange, for both the biogenesis of retroviral particles and a low-efficiency but mechanistically important mode of infection. This Trojan exosome hypothesis reconciles current paradigms of retrovirus-directed transmission with the unique lipid composition of retroviral particles, the host cell proteins present in retroviral particles, the complex cell biology of retroviral release, and the ability of retroviruses to infect cells independently of Envelope protein-receptor interactions. An exosomal origin also predicts that retroviruses pose an unsolvable paradox for adaptive immune responses, that retroviral antigen vaccines are unlikely to provide prophylactic protection, and that alloimmunity is a central component of antiretroviral immunity. Finally, the Trojan exosome hypothesis has important implications for the fight against HIV and AIDS, including how to develop new antiretroviral therapies, assess the risk of retroviral infection, and generate effective antiretroviral vaccines.

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Section: Evidence For the Antiretroviral Nature Of Alloimmunitysupporting

confidence: 54%

The Trojan exosome hypothesis

Gould

Booth

Hildreth³

2003

Proc. Natl. Acad. Sci. U.S.A.

563

486

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“…SIVsmlE660 was isolated by co-cultivation of CEM x 174 cells with spleen homogenate of a macaque that died of SIV-induced immunodeficiency [8]. This stock (SIV-Human) was used in previous efficacy studies of this WI-SIV vaccine [10,11]. A second stock was generated by passage of the SIV-Human stock in pigtailed macaque PBMC (SIV-Macaque).…”

Section: Challenge Virusesmentioning

confidence: 99%

Immunization with whole inactivated vaccine protects from infection by SIV grown in human but not macaque cells

Goldstein

Elkins

London

et al. 1994

J of Medical Primatology

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Homologous SIVsm stocks were generated by passage of a macaque isolate of SIVsm (SIVsm/E660) in human CEM x 174 cells or macaque peripheral blood mononuclear cells. Macaques were immunized with whole inactivated SIV vaccine consisting of virus generated by transfection of CEM x 174 cells with the SIVsmH4 clone and were challenged with either cell-free stock. Only vaccinees challenged with virus generated in human cells were protected from infection. This confirms the species-specificity of whole inactivated vaccine-mediated protection.

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“…Most attempts to develop candidate vaccines against lentivirus infections were without success (for a review, see reference 22). Nevertheless, in some experiments chimpanzees were successfully vaccinated against HIV type 1 (HIV-1) (4) and macaques were successfully vaccinated against HIV-2 or simian immunodeficiency virus (SIV) infections with candidate whole inactivated virus, live attenuated virus, recombinant virus, subunit virus vaccines, or combinations of these candidate vaccines (6,7,17,21,28,30,32,38). The mechanisms by which protective immunity was established in these systems are not well understood at present, although there are indications for a major role of both virusneutralizing (VN) antibodies and cell-mediated immunity (10,24,31).…”

mentioning

confidence: 99%

Enhancement of feline immunodeficiency virus infection after immunization with envelope glycoprotein subunit vaccines

Siebelink

Tijhaar

Huisman

et al. 1995

J Virol

108

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Cats were immunized three times with different recombinant feline immunodeficiency virus (FIV) candidate vaccines. Recombinant vaccinia virus (rVV)-expressed envelope glycoprotein with (vGR657) or without (vGR657x15) the cleavage site and an FIV envelope bacterial fusion protein (␤-Galactosidase-Env) were incorporated into immune-stimulating complexes or adjuvanted with Quil A. Although all immunized cats developed antibodies against the envelope protein, only the cats vaccinated with the rVV-expressed envelope glycoproteins developed antibodies which neutralized FIV infection of Crandell feline kidney cells. These antibodies failed to neutralize infection of thymocytes with a molecularly cloned homologous FIV. After the third immunization the cats were challenged with homologous FIV. Two weeks after challenge the cellassociated viral load proved to be significantly higher in the cats immunized with vGR657 and vGR657x15 than in the other cats. The cats immunized with vGR657 and vGR657x15 also developed antibodies against the Gag proteins more rapidly than the cats immunized with ␤-Galactosidase-Env or the control cats. This suggested that immunization with rVV-expressed glycoprotein of FIV results in enhanced infectivity of FIV. It was shown that the observed enhancement could be transferred to naive cats with plasma collected at the day of challenge.

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Inactivated Whole SIV Vaccine in Macaques: Evaluation of Protective Efficacy Against Challenge with Cell-Free Virus or Infected Cells

Cited by 23 publications

References 11 publications

The Trojan exosome hypothesis

The Trojan exosome hypothesis

Immunization with whole inactivated vaccine protects from infection by SIV grown in human but not macaque cells

Enhancement of feline immunodeficiency virus infection after immunization with envelope glycoprotein subunit vaccines

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