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2. Combination Adenovirus and Protein Vaccines Prevent Infection or Reduce Viral Burden after Heterologous Clade C Simian-Human Immunodeficiency Virus Mucosal Challenge

Author

Malherbe, Delphine C, Mendy, Jason, Vang, Lo, Barnette, Philip T, Reed, Jason, Lakhashe, Samir K, Owuor, Joshua, Gach, Johannes S, Legasse, Alfred W, Axthelm, Michael K, LaBranche, Celia C, Montefiori, David, Forthal, Donald N, Park, Byung, Wilson, James M, McLinden, James H, Xiang, Jinhua, Stapleton, Jack T, Sacha, Jonah B, Haynes, Barton F, Liao, Hua-Xin, Ruprecht, Ruth M, Smith, Jonathan, Gurwith, Marc, Haigwood, Nancy L, and Alexander, Jeff

Subjects
Vaccine Related, Prevention, HIV/AIDS, Infectious Diseases, Immunization, Vaccine Related (AIDS), Biotechnology, 3.4 Vaccines, Prevention of disease and conditions, and promotion of well-being, Infection, Good Health and Well Being, Adenoviridae, Animals, Antibodies, Neutralizing, Antibodies, Viral, Antibody Specificity, CD4 Lymphocyte Count, Cell Line, Genetic Vectors, Genotype, HIV, Humans, Immunity, Humoral, Kaplan-Meier Estimate, Macaca mulatta, Male, Protein Binding, SAIDS Vaccines, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus, T-Lymphocytes, Vaccines, Synthetic, Viral Envelope Proteins, Viral Load, HIV vaccine, adenovirus vector, V1V2-specific antibody, SHIV challenge, correlate of protection, rhesus macaque, simian human immunodeficiency virus, adenovirus, neutralizing antibody, vaccine, Simian immunodeficiency virus, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology
Abstract

HIV vaccine development is focused on designing immunogens and delivery methods that elicit protective immunity. We evaluated a combination of adenovirus (Ad) vectors expressing HIV 1086.C (clade C) envelope glycoprotein (Env), SIV Gag p55, and human pegivirus GBV-C E2 glycoprotein. We compared replicating simian (SAd7) with nonreplicating human (Ad4) adenovirus-vectored vaccines paired with recombinant proteins in a novel prime-boost regimen in rhesus macaques, with the goal of eliciting protective immunity against SHIV challenge. In both vaccine groups, plasma and buccal Env-specific IgG, tier 1 heterologous neutralizing antibodies, and antibody-dependent cell-mediated viral inhibition were readily generated. High Env-specific T cell responses elicited in all vaccinees were significantly greater than responses targeting Gag. After three intrarectal exposures to heterologous tier 1 clade C SHIV, all 10 sham-vaccinated controls were infected, whereas 4/10 SAd7- and 3/10 Ad4-vaccinated macaques remained uninfected or maintained tightly controlled plasma viremia. Time to infection was significantly delayed in SAd7-vaccinated macaques compared to the controls. Cell-associated and plasma virus levels were significantly lower in each group of vaccinated macaques compared to controls; the lowest plasma viral burden was found in animals vaccinated with the SAd7 vectors, suggesting superior immunity conferred by the replicating simian vectors. Furthermore, higher V1V2-specific binding antibody titers correlated with viral control in the SAd7 vaccine group. Thus, recombinant Ad plus protein vaccines generated humoral and cellular immunity that was effective in either protecting from SHIV acquisition or significantly reducing viremia in animals that became infected, consequently supporting additional development of replicating Ad vectors as HIV vaccines.IMPORTANCE There is a well-acknowledged need for an effective AIDS vaccine that protects against HIV infection and limits in vivo viral replication and associated pathogenesis. Although replicating virus vectors have been advanced as HIV vaccine platforms, there have not been any direct comparisons of the replicating to the nonreplicating format. The present study directly compared the replicating SAd7 to nonreplicating Ad4 vectors in macaques and demonstrated that in the SAd7 vaccine group, the time to infection was significantly delayed compared to the control group, and V1V2 Env-specific binding antibodies correlated with viral outcomes. Viral control was significantly enhanced in vaccinated macaques compared to controls, and in infected SAd7-vaccinated macaques compared to Ad4-vaccinated macaques, suggesting that this vector may have conferred more effective immunity. Because blocking infection is so difficult with current vaccines, development of a vaccine that can limit viremia if infection occurs would be valuable. These data support further development of replicating adenovirus vectors.

Published
2018

3. 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

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Prevention, Vaccine Related, Vaccine Related (AIDS), Pediatric Research Initiative, HIV/AIDS, Immunization, Infectious Diseases, Infection, Good Health and Well Being, Administration, Intravenous, Administration, Mucosal, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, HIV Antibodies, HIV-1, Humans, Immunity, Cellular, Immunity, Mucosal, Immunization, Passive, Immunoglobulin A, Immunoglobulin G, Macaca mulatta, Mucous Membrane, RNA, Viral, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus, T-Lymphocytes, IgA, IgG, Complete protection, Passive immunization, Rhesus monkey, SHIV-C mucosal challenge, Simian immunodeficiency virus, (6 max), Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Biomedical and clinical sciences, Health sciences
Abstract

Although IgA is the most abundantly produced immunoglobulin in humans, its role in preventing HIV-1 acquisition, which occurs mostly via mucosal routes, remains unclear. In our passive mucosal immunizations of rhesus macaques (RMs), the anti-HIV-1 neutralizing monoclonal antibody (nmAb) HGN194, given either as dimeric IgA1 (dIgA1) or dIgA2 intrarectally (i.r.), protected 83% or 17% of the RMs against i.r. simian-human immunodeficiency virus (SHIV) challenge, respectively. Data from the RV144 trial implied that vaccine-induced plasma IgA counteracted the protective effector mechanisms of IgG1 with the same epitope specificity. We thus hypothesized that mucosal dIgA2 might diminish the protection provided by IgG1 mAbs targeting the same epitope. To test our hypothesis, we administered HGN194 IgG1 intravenously (i.v.) either alone or combined with i.r. HGN194 dIgA2. We enrolled SHIV-exposed, persistently aviremic RMs protected by previously administered nmAbs; RM anti-human IgG responses were undetectable. However, low-level SIV Gag-specific proliferative T-cell responses were found. These animals resemble HIV-exposed, uninfected humans, in which local and systemic cellular immune responses have been observed. HGN194 IgG1 and dIgA2 used alone and the combination of the two neutralized the challenge virus equally well in vitro. All RMs given only i.v. HGN194 IgG1 became infected. In contrast, all RMs given HGN194 IgG1+dIgA2 were completely protected against high-dose i.r. SHIV-1157ipEL-p challenge. These data imply that combining suboptimal defenses at the mucosal and systemic levels can completely prevent virus acquisition. Consequently, active vaccination should focus on defense-in-depth, a strategy that seeks to build up defensive fall-back positions well behind the fortified frontline.

Published
2015

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

6. Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose

Author

Sholukh, Anton M, Byrareddy, Siddappa N, Shanmuganathan, Vivekanandan, Hemashettar, Girish, Lakhashe, Samir K, Rasmussen, Robert A, Watkins, Jennifer D, Vyas, Hemant K, Thorat, Swati, Brandstoetter, Tania, Mukhtar, Muhammad M, Yoon, John K, Novembre, Francis J, Villinger, Francois, Landucci, Gary, Forthal, Donald N, Ratcliffe, Sarah, Tuero, Iskra, Robert-Guroff, Marjorie, Polonis, Victoria R, Bilska, Miroslawa, Montefiori, David C, Johnson, Welkin E, Ertl, Hildegund C, and Ruprecht, Ruth M

Subjects
Macaque model, Heterologous R5 SHIV clade C challenge, SHIVIG, Passive immunization, Enhancement of infection, Non-human primate model
Abstract

BackgroundA key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG.ResultsSHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG.ConclusionOur primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter.

Published
2014

7. The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells

Author

Gupta, Sandeep, Gach, Johannes S, Becerra, Juan C, Phan, Tran B, Pudney, Jeffrey, Moldoveanu, Zina, Joseph, Sarah B, Landucci, Gary, Supnet, Medalyn Jude, Ping, Li-Hua, Corti, Davide, Moldt, Brian, Hel, Zdenek, Lanzavecchia, Antonio, Ruprecht, Ruth M, Burton, Dennis R, Mestecky, Jiri, Anderson, Deborah J, Forthal, Donald N, and Desrosiers, Ronald C

Subjects
Antibody-Dependent Enhancement, Female Genital-Tract, Monoclonal-Antibodies, Dendritic Cells, Hiv-1-Infected Individuals, 1-Infected Individuals, Mediated Presentation, Cervical Ectopy, Human Placenta, Vaginal Ph
Published
2013

8. Prior exposure to an attenuated Listeria vaccine does not reduce immunogenicity: pre-clinical assessment of the efficacy of a Listeria vaccine in the induction of immune responses against HIV

Author

Whitney, James B, Mirshahidi, Saied, Lim, So-Yon, Goins, Lauren, Ibegbu, Chris C, Anderson, Daniel C, Raybourne, Richard B, Frankel, Fred R, Lieberman, Judy, and Ruprecht, Ruth M

Abstract

Abstract Background We have evaluated an attenuated Listeria monocytogenes (Lm) candidate vaccine vector in nonhuman primates using a delivery regimen relying solely on oral vaccination. We sought to determine the impact of prior Lm vector exposure on the development of new immune responses against HIV antigens. Findings Two groups of rhesus macaques one Lm naive, the other having documented prior Lm vector exposures, were evaluated in response to oral inoculations of the same vector expressing recombinant HIV-1 Gag protein. The efficacy of the Lm vector was determined by ELISA to assess the generation of anti-Listerial antibodies; cellular responses were measured by HIV-Gag specific ELISpot assay. Our results show that prior Lm exposures did not diminish the generation of de novo cellular responses against HIV, as compared to Listeria-naïve monkeys. Moreover, empty vector exposures did not elicit potent antibody responses, consistent with the intracellular nature of Lm. Conclusions The present study demonstrates in a pre-clinical vaccine model, that prior oral immunization with an empty Lm vector does not diminish immunogenicity to Lm-expressed HIV genes. This work underscores the need for the continued development of attenuated Lm as an orally deliverable vaccine.

Published
2011

11. Intranasal vaccination with lipid-conjugated immunogens promotes antigen transmucosal uptake to drive mucosal and systemic immunity

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Hartwell, Brittany L, Melo, Mariane B, Xiao, Peng, Lemnios, Ashley A, Li, Na, Chang, Jason YH, Yu, Jingyou, Gebre, Makda S, Chang, Aiquan, Maiorino, Laura, Carter, Crystal, Moyer, Tyson J, Dalvie, Neil C, Rodriguez-Aponte, Sergio A, Rodrigues, Kristen A, Silva, Murillo, Suh, Heikyung, Adams, Josetta, Fontenot, Jane, Love, J Christopher, Barouch, Dan H, Villinger, Francois, Ruprecht, Ruth M, Irvine, Darrell J, Massachusetts Institute of Technology. Department of Biological Engineering, Hartwell, Brittany L, Melo, Mariane B, Xiao, Peng, Lemnios, Ashley A, Li, Na, Chang, Jason YH, Yu, Jingyou, Gebre, Makda S, Chang, Aiquan, Maiorino, Laura, Carter, Crystal, Moyer, Tyson J, Dalvie, Neil C, Rodriguez-Aponte, Sergio A, Rodrigues, Kristen A, Silva, Murillo, Suh, Heikyung, Adams, Josetta, Fontenot, Jane, Love, J Christopher, Barouch, Dan H, Villinger, Francois, Ruprecht, Ruth M, and Irvine, Darrell J

Abstract

To combat the HIV epidemic and emerging threats such as SARS-CoV-2, immunization strategies are needed that elicit protection at mucosal portals of pathogen entry. Immunization directly through airway surfaces is effective in driving mucosal immunity, but poor vaccine uptake across the mucus and epithelial lining is a limitation. The major blood protein albumin is constitutively transcytosed bidirectionally across the airway epithelium through interactions with neonatal Fc receptors (FcRn). Exploiting this biology, here, we demonstrate a strategy of “albumin hitchhiking” to promote mucosal immunity using an intranasal vaccine consisting of protein immunogens modified with an amphiphilic albumin-binding polymer-lipid tail, forming amph-proteins. Amph-proteins persisted in the nasal mucosa of mice and nonhuman primates and exhibited increased uptake into the tissue in an FcRn-dependent manner, leading to enhanced germinal center responses in nasal-associated lymphoid tissue. Intranasal immunization with amph-conjugated HIV Env gp120 or SARS-CoV-2 receptor binding domain (RBD) proteins elicited 100- to 1000-fold higher antigen-specific IgG and IgA titers in the serum, upper and lower respiratory mucosa, and distal genitourinary mucosae of mice compared to unmodified protein. Amph-RBD immunization induced high titers of SARS-CoV-2–neutralizing antibodies in serum, nasal washes, and bronchoalveolar lavage. Furthermore, intranasal amph-protein immunization in rhesus macaques elicited 10-fold higher antigen-specific IgG and IgA responses in the serum and nasal mucosa compared to unmodified protein, supporting the translational potential of this approach. These results suggest that using amph-protein vaccines to deliver antigen across mucosal epithelia is a promising strategy to promote mucosal immunity against HIV, SARS-CoV-2, and other infectious diseases.

Published
2023

13. 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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14. 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

18. 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

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

Published
2022
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20. 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
AIDS Vaccines, Virosomes, Immunoglobulin G, HIV Seropositivity, Immunology, HIV-1, Animals, Humans, Immunology and Allergy, Female, Simian Immunodeficiency Virus, Macaca mulatta, Immunoglobulin A
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.

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

Author

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

Published
2021
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25. 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

32. 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

34. Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges

Author

Gong, Siqi, primary, Lakhashe, Samir K., additional, Hariraju, Dinesh, additional, Scinto, Hanna, additional, Lanzavecchia, Antonio, additional, Cameroni, Elisabetta, additional, Corti, Davide, additional, Ratcliffe, Sarah J., additional, Rogers, Kenneth A., additional, Xiao, Peng, additional, Fontenot, Jane, additional, Villinger, François, additional, and Ruprecht, Ruth M., additional

Published
2021
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36. PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure

Author

Taylor, Roslyn A., primary, Xiao, Sixia, additional, Carias, Ann M., additional, McRaven, Michael D., additional, Thakkar, Divya N., additional, Araínga, Mariluz, additional, Allen, Edward J., additional, Rogers, Kenneth A., additional, Kumarapperuma, Sidath C., additional, Gong, Siqi, additional, Fought, Angela J., additional, Anderson, Meegan R., additional, Thomas, Yanique, additional, Schneider, Jeffrey R., additional, Goins, Beth, additional, Fox, Peter, additional, Villinger, Francois J., additional, Ruprecht, Ruth M., additional, and Hope, Thomas J., additional

Published
2021
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37. Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates

Author

Koch Institute for Integrative Cancer Research at MIT, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Materials Science and Engineering, Martin, Jacob T, Hartwell, Brittany L, Kumarapperuma, Sidath C, Melo, Mariane B, Carnathan, Diane G, Cossette, Benjamin J, Adams, Josetta, Gong, Siqi, Zhang, Wei, Tokatlian, Talar, Menis, Sergey, Schiffner, Torben, Franklin, Crystal G, Goins, Beth, Fox, Peter T, Silvestri, Guido, Schief, William R, Ruprecht, Ruth M, Irvine, Darrell J, Koch Institute for Integrative Cancer Research at MIT, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Materials Science and Engineering, Martin, Jacob T, Hartwell, Brittany L, Kumarapperuma, Sidath C, Melo, Mariane B, Carnathan, Diane G, Cossette, Benjamin J, Adams, Josetta, Gong, Siqi, Zhang, Wei, Tokatlian, Talar, Menis, Sergey, Schiffner, Torben, Franklin, Crystal G, Goins, Beth, Fox, Peter T, Silvestri, Guido, Schief, William R, Ruprecht, Ruth M, and Irvine, Darrell J

Abstract

Antigen accumulation in lymph nodes (LNs) is critical for vaccine efficacy, but understanding of vaccine biodistribution in humans or large animals remains limited. Using the rhesus macaque model, we employed a combination of positron emission tomography (PET) and fluorescence imaging to characterize the whole-animal to tissue-level biodistribution of a subunit vaccine comprised of an HIV envelope trimer protein nanoparticle (trimer-NP) and lipid-conjugated CpG adjuvant (amph-CpG). Following immunization in the thigh, PET imaging revealed vaccine uptake primarily in inguinal and iliac LNs, reaching distances up to 17 cm away from the injection site. Within LNs, trimer-NPs exhibited striking accumulation on the periphery of follicular dendritic cell (FDC) networks in B cell follicles. Comparative imaging of soluble Env trimers (not presented on nanoparticles) in naïve or previously-immunized animals revealed diffuse deposition of trimer antigens in LNs following primary immunization, but concentration on FDCs in pre-immunized animals with high levels of trimer-specific IgG. These data demonstrate the capacity of nanoparticle or "albumin hitchhiking" technologies to concentrate vaccines in genitourinary tract-draining LNs, which may be valuable for promoting mucosal immunity.

Published
2021

39. Modified Adenovirus Prime-Protein Boost Clade C HIV Vaccine Strategy Results in Reduced Viral DNA in Blood and Tissues Following Tier 2 SHIV Challenge

Author

Malherbe, Delphine C., primary, Vang, Lo, additional, Mendy, Jason, additional, Barnette, Philip T., additional, Spencer, David A., additional, Reed, Jason, additional, Kareko, Bettie W., additional, Sather, D. Noah, additional, Pandey, Shilpi, additional, Wibmer, Constantinos K., additional, Robins, Harlan, additional, Fuller, Deborah H., additional, Park, Byung, additional, Lakhashe, Samir K., additional, Wilson, James M., additional, Axthelm, Michael K., additional, Ruprecht, Ruth M., additional, Moore, Penny L., additional, Sacha, Jonah B., additional, Hessell, Ann J., additional, Alexander, Jeff, additional, and Haigwood, Nancy L., additional

Published
2021
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42. 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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45. Correction: ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type

Author

Schifanella, Luca, primary, Barnett, Susan W., additional, Bissa, Massimiliano, additional, Galli, Veronica, additional, Doster, Melvin N., additional, Vaccari, Monica, additional, Tomaras, Georgia D., additional, Shen, Xiaoying, additional, Phogat, Sanjay, additional, Pal, Ranajit, additional, Montefiori, David C., additional, LaBranche, Celia C., additional, Rao, Mangala, additional, Trinh, Hung V., additional, Washington-Parks, Robyn, additional, Liyanage, Namal P. M., additional, Gorini, Giacomo, additional, Brown, Dallas R., additional, Liang, Frank, additional, Loré, Karin, additional, Venzon, David J., additional, Magnanelli, William, additional, Metrinko, Michelle, additional, Kramer, Josh, additional, Breed, Matthew, additional, Alter, Galit, additional, Ruprecht, Ruth M., additional, and Franchini, Genoveffa, additional

Published
2020
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46. Immunotherapy with DNA vaccine and live attenuated rubella/SIV gag vectors plus early ART can prevent SIVmac251 viral rebound in acutely infected rhesus macaques

Author

Virnik, Konstantin, primary, Rosati, Margherita, additional, Medvedev, Alexei, additional, Scanlan, Aaron, additional, Walsh, Gabrielle, additional, Dayton, Frances, additional, Broderick, Kate E., additional, Lewis, Mark, additional, Bryson, Yvonne, additional, Lifson, Jeffrey D., additional, Ruprecht, Ruth M., additional, Felber, Barbara K., additional, and Berkower, Ira, additional

Published
2020
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