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4. Defense-in-depth by mucosally administered anti-HIV dimeric IgA2 and systemic IgG1 mAbs: Complete protection of rhesus monkeys from mucosal SHIV challenge

Author

Sholukh, Anton M., Watkins, Jennifer D., Vyas, Hemant K., Gupta, Sandeep, Lakhashe, Samir K., Thorat, Swati, Zhou, Mingkui, Hemashettar, Girish, Bachler, Barbara C., Forthal, Donald N., Villinger, Francois, Sattentau, Quentin J., Weiss, Robin A., Agatic, Gloria, Corti, Davide, Lanzavecchia, Antonio, Heeney, Jonathan L., and Ruprecht, Ruth M.

Published
2015
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5. Multimodality vaccination against clade C SHIV: Partial protection against mucosal challenges with a heterologous tier 2 virus

Author

Lakhashe, Samir K., Byrareddy, Siddappa N., Zhou, Mingkui, Bachler, Barbara C., Hemashettar, Girish, Hu, Shiu-Lok, Villinger, Francois, Else, James G., Stock, Shannon, Lee, Sandra J., Vargas-Inchaustegui, Diego A., Cofano, Egidio Brocca, Robert-Guroff, Marjorie, Johnson, Welkin E., Polonis, Victoria R., Forthal, Donald N., Loret, Erwann P., Rasmussen, Robert A., and Ruprecht, Ruth M.

Published
2014
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6. Impact of antibody quality and anamnestic response on viremia control post-challenge in a combined Tat/Env vaccine regimen in rhesus macaques

Author

Demberg, Thorsten, Brocca-Cofano, Egidio, Kuate, Seraphin, Aladi, Stanley, Vargas-Inchaustegui, Diego A., Venzon, David, Kalisz, Irene, Kalyanaraman, V.S., Lee, Eun Mi, Pal, Ranajit, DiPasquale, Janet, Ruprecht, Ruth M., Montefiori, David C., Srivastava, Indresh, Barnett, Susan W., and Robert-Guroff, Marjorie

Published
2013
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7. Attenuated HIV Vaccine: Caveats

Author

Ruprecht, Ruth M., Baba, Timothy W., Liska, Vladimir, Deacon, N. J., McPhee, D. A., Crowe, S., Learmont, J., and Mills, J.

Published
1996

9. Relative Transmissibility of an R5 Clade C Simian-Human Immunodeficiency Virus Across Different Mucosae in Macaques Parallels the Relative Risks of Sexual HIV-1 Transmission in Humans via Different Routes

Author

Chenine, Agnès L., Siddappa, Nagadenahalli B., Kramer, Victor G., Sciaranghella, Gaia, Rasmussen, Robert A., Lee, Sandra J., Santosuosso, Michael, Poznansky, Mark C., Velu, Vijayakumar, Amara, Rama R., Souder, Chris, Anderson, Daniel C., Villinger, François, Else, James G., Novembre, Francis J., Strobert, Elizabeth, O'Neil, Shawn P., Secor, W. Evan, and Ruprecht, Ruth M.

Published
2010

11. Prime–boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein: Efficacy against repeated mucosal R5 clade C SHIV challenges

Author

Lakhashe, Samir K., Velu, Vijayakumar, Sciaranghella, Gaia, Siddappa, Nagadenahalli B., DiPasquale, Janet M., Hemashettar, Girish, Yoon, John K., Rasmussen, Robert A., Yang, Feng, Lee, Sandra J., Montefiori, David C., Novembre, Francis J., Villinger, François, Amara, Rama Rao, Kahn, Maria, Hu, Shiu-Lok, Li, Sufen, Li, Zhongxia, Frankel, Fred R., Robert-Guroff, Marjorie, Johnson, Welkin E., Lieberman, Judy, and Ruprecht, Ruth M.

Published
2011
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17. Oral Transmission of Primate Lentiviruses

Author

Ruprecht, Ruth M., Baba, Timothy W., Liska, Vladimir, Ray, Nancy B., Martin, Louis N., Murphey-Corb, Michael, Rizvi, Tahir A., Bernacky, Bruce J., Keeling, Michale E., McClure, Harold M., and Andersen, Janet

Published
1999

22. Attenuated Retrovirus Vaccines and AIDS

Author

Spinner, Abbie, Otsyula, Moses, McChesney, Michael B., Marthas, Marta L., Shearer, Gene M., Lucey, Daniel R., Clerici, Mario, Kestler, Harry W., Jeang, Kuan-Teh, Marx, Preston A., Baba, Timothy W., Liska, Vladimir, Hu, Yuwen, Rasmussen, Robert A., Pennick, Dominique, Bronson, Rod, Greene, Michael F., and Ruprecht, Ruth M.

Published
1995

32. Antibody Light Chains: Key to Increased Monoclonal Antibody Yields in Expi293 Cells?

Author

Gong, Siqi, Gautam, Seijal, Coneglio, Joshua D., Scinto, Hanna B., and Ruprecht, Ruth M.

Subjects
MONOCLONAL antibodies, IMMUNOGLOBULINS
Abstract

When constructing isogenic recombinant IgM–IgG pairs, we discovered that μ heavy chains strongly prefer partnering with λ light chains for optimal IgM expression in transiently cotransfected Expi293 cells. When μ chains were paired with κ light chains, IgM yields were low but increased by logs—up to 20,000 X—by using λ chains instead. Switching light chains did not alter epitope specificity. For dimeric IgA2, optimal expression involved pairing with λ chains, whereas light-chain preference varied for other immunoglobulin classes. In summary, recombinant IgM production can be drastically increased by using λ chains, an important finding in the use of IgM for mucosal immunoprophylaxis. [ABSTRACT FROM AUTHOR]

Published
2022
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35. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian–human immunodeficiency virus infection

Author

Baba, Timothy W., Liska, Vladimir, Hofmann-Lehmann, Regina, Vlasak, Josef, Xu, Weidong, Ayehunie, Seyoum, Cavacini, Lisa A., Posner, Marshall R., Katinger, Hermann, Stiegler, Gabriela, Bernacky, Bruce J., Rizvi, Tahir A., Schmidt, Russell, Hill, Lori R., Keeling, Michale E., Lu, Yichen, Wright, Joel E., Chou, Ting-Chao, and Ruprecht, Ruth M.

Published
2000
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36. RNA interference -- a new weapon against HIV and beyond

Author

Kitabwalla, Moiz and Ruprecht, Ruth M.

Subjects
Anti-HIV agents -- Research
Abstract

The development of drug resistance in HIV has prompted scientists to develop drugs that interfere with viral RNA. These include small interfering RNA, interferon, antisense RNA, and ribozymes. These drugs can degrade messenger RNA and the viral genome itself.

Published
2002

42. Cooperation Between Systemic and Mucosal Antibodies Induced by Virosomal Vaccines Targeting HIV-1 Env: Protection of Indian Rhesus Macaques Against Low-Dose Intravaginal SHIV Challenges.

Author

Lakhashe, Samir K., Amacker, Mario, Hariraju, Dinesh, Vyas, Hemant K., Morrison, Kyle S., Weiner, Joshua A., Ackerman, Margaret E., Roy, Vicky, Alter, Galit, Ferrari, Guido, Montefiori, David C., Tomaras, Georgia D., Sawant, Sheetal, Yates, Nicole L., Gast, Chris, Fleury, Sylvain, and Ruprecht, Ruth M.

Subjects
RHESUS monkeys, IMMUNOGLOBULINS, VACCINE effectiveness, IMMUNE response, HIV
Abstract

A virosomal vaccine inducing systemic/mucosal anti-HIV-1 gp41 IgG/IgA had previously protected Chinese-origin rhesus macaques (RMs) against vaginal SHIVSF162P3 challenges. Here, we assessed its efficacy in Indian-origin RMs by intramuscular priming/intranasal boosting (n=12/group). Group K received virosome-P1-peptide alone (harboring the Membrane Proximal External Region), Group L combined virosome-rgp41 plus virosome-P1, and Group M placebo virosomes. Vaccination induced plasma binding but no neutralizing antibodies. Five weeks after boosting, all RMs were challenged intravaginally with low-dose SHIVSF162P3 until persistent systemic infection developed. After SHIV challenge #7, six controls were persistently infected versus only one Group L animal (vaccine efficacy 87%; P =0.0319); Group K was not protected. After a 50% SHIV dose increase starting with challenge #8, protection in Group L was lost. Plasmas/sera were analyzed for IgG phenotypes and effector functions; the former revealed that protection in Group L was significantly associated with increased binding to FcγR2/3(A/B) across several time-points, as were some IgG measurements. Vaginal washes contained low-level anti-gp41 IgGs and IgAs, representing a 1-to-5-fold excess over the SHIV inoculum's gp41 content, possibly explaining loss of protection after the increase in challenge-virus dose. Virosomal gp41-vaccine efficacy was confirmed during the initial seven SHIV challenges in Indian-origin RMs when the SHIV inoculum had at least 100-fold more HIV RNA than acutely infected men's semen. Vaccine protection by virosome-induced IgG and IgA parallels the cooperation between systemically administered IgG1 and mucosally applied dimeric IgA2 monoclonal antibodies that as single-agents provided no/low protection – but when combined, prevented mucosal SHIV transmission in all passively immunized RMs. [ABSTRACT FROM AUTHOR]

Published
2022
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48. Localization of infection in neonatal rhesus macaques after oral viral challenge.

Author

Taylor, Roslyn A., McRaven, Michael D., Carias, Ann M., Anderson, Meegan R., Matias, Edgar, Araínga, Mariluz, Allen, Edward J., Rogers, Kenneth A., Gupta, Sandeep, Kulkarni, Viraj, Lakhashe, Samir, Lorenzo-Redondo, Ramon, Thomas, Yanique, Strickland, Amanda, Villinger, Francois J., Ruprecht, Ruth M., and Hope, Thomas J.

Subjects
RHESUS monkeys, NEONATAL infections, MACAQUES, GENETIC vectors, VIRUS diseases, POSITRON emission tomography, SMALL intestine
Abstract

Vertical transmission of human immunodeficiency virus (HIV) can occur in utero, during delivery, and through breastfeeding. We utilized Positron Emission Tomography (PET) imaging coupled with fluorescent microscopy of 64Cu-labeled photoactivatable-GFP-HIV (PA-GFP-BaL) to determine how HIV virions distribute and localize in neonatal rhesus macaques two and four hours after oral viral challenge. Our results show that by four hours after oral viral exposure, HIV virions localize to and penetrate the rectal mucosa. We also used a dual viral challenge with a non-replicative viral vector and a replication competent SHIV-1157ipd3N4 to examine viral transduction and dissemination at 96 hours. Our data show that while SHIV-1157ipd3N4 infection can be found in the oral cavity and upper gastrointestinal (GI) tract, the small and large intestine contained the largest number of infected cells. Moreover, we found that T cells were the biggest population of infected immune cells. Thus, thanks to these novel technologies, we are able to visualize and delineate of viral distribution and infection throughout the entire neonatal GI tract during acute viral infection. Author summary: Approximately 1.8 million children are currently living with human immunodeficiency virus (HIV). While mother-to-child HIV transmission can occur in utero and during delivery, it most commonly occurs through breastfeeding, creating the need to understand how the virus moves throughout the body and infects the infant once breast milk is consumed. Here, we used multiple imaging techniques and PCR to determine how HIV distributes throughout the gastrointestinal tract after oral viral exposure and in which tissues and cell types become acutely infected. We found that HIV rapidly spreads throughout and penetrates the entire gastrointestinal tract as early as four hours after exposure. We also found that the intestine contained the largest number of infected cells at 96 hours and that most cells infected were T cells. Our study shows that these imaging technologies allow for the examination of viral distribution and infection in a rhesus macaque model. [ABSTRACT FROM AUTHOR]

Published
2021
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49. Attenuated retrovirus vaccines and AIDS

Author

Van Rompay, Koen K.A., Spinner, Abbie, Otsyula, Moses, McChesney, Michael B., Marthas, Marta L., Shearer, Gene M., Lucey, Daniel R., Clerici, Mario, Kestler, Harry W., Jeang, Kuan-Teh, Marx, Preston, Buba, Timothy W., Liska, Vladimir, Hu, Yuwen, Rasmussen, Robert A., Penninck, Dominique, Bronson, Rod, Greene, Michael F., and Ruprecht, Ruth M.

Subjects
AIDS vaccines -- Research, Simian immunodeficiency virus -- Research, Science and technology, Research
Abstract

In their recent report, Timothy W. Baba et al. state that a deletion mutant of simian immunodeficiency virus (SIVδ3), which does not cause disease in adult macaques and has been [...]

Published
1995

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