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1. Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial.

Author

Branche, Angela, Rouphael, Nadine, Diemert, David, Falsey, Ann, Losada, Cecilia, Baden, Lindsey, Frey, Sharon, Whitaker, Jennifer, Anderson, Evan, Walter, Emmanuel, Novak, Richard, Rupp, Richard, Jackson, Lisa, Babu, Tara, Kottkamp, Angelica, Luetkemeyer, Anne, Immergluck, Lilly, Presti, Rachel, Bäcker, Martín, Winokur, Patricia, Mahgoub, Siham, Goepfert, Paul, Fusco, Dahlene, Malkin, Elissa, Bethony, Jeffrey, Walsh, Edward, Graciaa, Daniel, Samaha, Hady, Sherman, Amy, Walsh, Stephen, Abate, Getahun, Oikonomopoulou, Zacharoula, El Sahly, Hana, Kamidani, Satoshi, Smith, Michael, Ladner, Benjamin, Porterfield, Laura, Dunstan, Maya, Wald, Anna, Davis, Tamia, Atmar, Robert, Mulligan, Mark, Lyke, Kirsten, Posavad, Christine, Meagher, Megan, Stephens, David, Neuzil, Kathleen, Abebe, Kuleni, Hill, Heather, Albert, Jim, Telu, Kalyani, Mu, Jinjian, Lewis, Teri, Giebeig, Lisa, Eaton, Amanda, Netzl, Antonia, Wilks, Samuel, Türeli, Sina, Makhene, Mamodikoe, Crandon, Sonja, Montefiori, David, Makowski, Mat, Smith, Derek, Nayak, Seema, Roberts, Paul, Beigel, John, Little, Susan, and Martin, Thomas

Subjects
Humans, COVID-19 Vaccines, SARS-CoV-2, COVID-19, Broadly Neutralizing Antibodies
Abstract

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 .

Published
2023

2. Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study

Author

Ozonoff, Al, Jayavelu, Naresh Doni, Liu, Shanshan, Melamed, Esther, Milliren, Carly E., Qi, Jingjing, Geng, Linda N., McComsey, Grace A., Cairns, Charles B., Baden, Lindsey R., Schaenman, Joanna, Shaw, Albert C., Samaha, Hady, Seyfert-Margolis, Vicki, Krammer, Florian, Rosen, Lindsey B., Steen, Hanno, Syphurs, Caitlin, Dandekar, Ravi, Shannon, Casey P., Sekaly, Rafick P., Ehrlich, Lauren I. R., Corry, David B., Kheradmand, Farrah, Atkinson, Mark A., Brakenridge, Scott C., Higuita, Nelson I. Agudelo, Metcalf, Jordan P., Hough, Catherine L., Messer, William B., Pulendran, Bali, Nadeau, Kari C., Davis, Mark M., Sesma, Ana Fernandez, Simon, Viviana, van Bakel, Harm, Kim-Schulze, Seunghee, Hafler, David A., Levy, Ofer, Kraft, Monica, Bime, Chris, Haddad, Elias K., Calfee, Carolyn S., Erle, David J., Langelier, Charles R., Eckalbar, Walter, Bosinger, Steven E., Peters, Bjoern, Kleinstein, Steven H., Reed, Elaine F., Augustine, Alison D., Diray-Arce, Joann, Maecker, Holden T., Altman, Matthew C., Montgomery, Ruth R., Becker, Patrice M., and Rouphael, Nadine

Published
2024
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4. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients

Author

Abraham, James, Adkisson, Michael, Albert, Marisa, Altamirano, Luz Torres, Alvarenga, Bonny, Anderson, Matthew L., Anderson, Evan J., Arnett, Azlann, Asashima, Hiromitsu, Atkinson, Mark A., Baden, Lindsey R., Barton, Brenda, Beach, Katherine, Beagle, Elizabeth, Becker, Patrice M., Bell, Matthew R., Bernui, Mariana, Bime, Christian, Boddapati, Arun Kumar, Booth, J. Leland, Borresen, Brittney, Brakenridge, Scott C., Bristow, Laurel, Bryant, Robert, Calfee, Carolyn S., Carreño, Juan Manuel, Carrillo, Sidney, Chak, Suzanna, Chang, Iris, Connors, Jennifer, Conway, Michelle, Corry, David B., Cowan, David, Croen, Brett, Dela Cruz, Charles S., Cusimano, Gina, Eaker, Lily, Edwards, Carolyn, Ehrlich, Lauren I.R., Elashoff, David, Erickson, Heidi, Erle, David J., Farhadian, Shelli, Farrugia, Keith, Fatou, Benoit, Fernandes, Andrea, Fernandez-Sesma, Ana, Fragiadakis, Gabriela K., Furukawa, Sara, Geltman, Janelle N., Ghale, Rajani, Bermúdez González, Maria Carolina, Goonewardene, I. Michael, Guerrero, Estella Sanchez, Guirgis, Faheem W., Hafler, David A., Hamilton, Sydney, Harris, Paul, Hayati, Arash Nemati, Hendrickson, Carolyn M., Agudelo Higuita, Nelson I., Hodder, Thomas, Holland, Steven M., Hough, Catherine L., Huerta, Christopher, Hurley, Kerin C., Hutton, Scott R., Iwasaki, Akiko, Jauregui, Alejandra, Jha, Meenakshi, Johnson, Brandi, Joyner, David, Kangelaris, Kirsten N., Kelly, Geoffrey, Khalil, Zain, Khan, Zenab, Kheradmand, Farrah, Kim, James N., Kimura, Hiroki, Ko, Albert I., Kohr, Bernard, Kraft, Monica, Krummel, Matthew, Kutzler, Michele A., Lasky-Su, Jessica, Lee, Serena, Lee, Deanna, Leipold, Michael, Lentucci, Claudia, Leroux, Carolyn, Lin, Edward, Liu, Shanshan, Love, Christina, Lu, Zhengchun, Maliskova, Lenka, Manning, Brittany Roth, Manohar, Monali, Martens, Mark, McComsey, Grace A., McEnaney, Kerry, McLin, Renee, Melamed, Esther, Melnyk, Nataliya, Mendez, Kevin, Messer, William B., Metcalf, Jordan P., Michelotti, Gregory, Mick, Eran, Mohanty, Subhasis, Mosier, Jarrod, Mulder, Lubbertus C.F., Murphy, Maimouna, Nadeau, Kari R.C., Nelson, Ebony, Nelson, Allison, Nguyen, Viet, Oberhaus, Jordan, Panganiban, Bernadine, Pellegrini, Kathryn L., Pickering, Harry C., Powell, Debra L., Presnell, Scott, Pulendran, Bali, Rahman, Adeeb H., Rashid, Ahmad Sadeed, Raskin, Ariel, Reed, Elaine F., Ribeiro, Susan Pereira, Rivera, Adreanne M., Rogers, Jacob E., Rogers, Angela, Rogowski, Brandon, Rooks, Rebecca, Rosenberg-Hasson, Yael, Rothman, Jessica, Rousseau, Justin F., Salehi-Rad, Ramin, Saluvan, Mehmet, Samaha, Hady, Schaenman, Joanna, Schunk, Ron, Semenza, Nicholas C., Sen, Subha, Sevransky, Jonathan, Seyfert-Margolis, Vicki, Shaheen, Tanzia, Shaw, Albert C., Sieg, Scott, Siegel, Sarah A.R., Sigal, Natalia, Siles, Nadia, Simmons, Brent, Simon, Viviana, Singh, Gagandeep, Sinko, Lauren, Smith, Cecilia M., Smolen, Kinga K., Song, Li-Zhen, Srivastava, Komal, Sullivan, Peter, Syphurs, Caitlin, Tcheou, Johnstone, Tegos, George P., Tharp, Greg K., Tong, Alexandra, Tsitsiklis, Alexandra, Ungaro, Ricardo F., Vaysman, Tatyana, Viode, Arthur, Vita, Randi, Wang, Xiaomei, Ward, Alyssa, Ward, Dawn C., Willmore, Andrew, Woloszczuk, Kyra, Wong, Kari, Woodruff, Prescott G., Xu, Leqi, van Haren, Simon, van de Guchte, Adriana, Zhao, Yujiao, Diray-Arce, Joann, Fourati, Slim, Doni Jayavelu, Naresh, Patel, Ravi, Maguire, Cole, Chang, Ana C., Dandekar, Ravi, Qi, Jingjing, Lee, Brian H., van Zalm, Patrick, Schroeder, Andrew, Chen, Ernie, Konstorum, Anna, Brito, Anderson, Gygi, Jeremy P., Kho, Alvin, Chen, Jing, Pawar, Shrikant, Gonzalez-Reiche, Ana Silvia, Hoch, Annmarie, Milliren, Carly E., Overton, James A., Westendorf, Kerstin, Cairns, Charles B., Rouphael, Nadine, Bosinger, Steven E., Kim-Schulze, Seunghee, Krammer, Florian, Rosen, Lindsey, Grubaugh, Nathan D., van Bakel, Harm, Wilson, Michael, Rajan, Jayant, Steen, Hanno, Eckalbar, Walter, Cotsapas, Chris, Langelier, Charles R., Levy, Ofer, Altman, Matthew C., Maecker, Holden, Montgomery, Ruth R., Haddad, Elias K., Sekaly, Rafick P., Esserman, Denise, Ozonoff, Al, Augustine, Alison D., Guan, Leying, Peters, Bjoern, and Kleinstein, Steven H.

Published
2023
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5. Persistent SARS-CoV-2–specific immune defects in kidney transplant recipients following third mRNA vaccine dose

Author

Werbel, William A., Karaba, Andrew H., Chiang, Teresa Po-Yu, Massie, Allan B., Brown, Diane M., Watson, Natasha, Chahoud, Maggie, Thompson, Elizabeth A., Johnson, Aileen C., Avery, Robin K., Cochran, Willa V., Warren, Daniel, Liang, Tao, Fribourg, Miguel, Huerta, Christopher, Samaha, Hady, Klein, Sabra L., Bettinotti, Maria P., Clarke, William A., Sitaras, Ioannis, Rouphael, Nadine, Cox, Andrea L., Bailey, Justin R., Pekosz, Andrew, Tobian, Aaron A.R., Durand, Christine M., Bridges, Nancy D., Larsen, Christian P., Heeger, Peter S., and Segev, Dorry L.

Published
2023
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6. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study

Author

Ozonoff, Al, Schaenman, Joanna, Jayavelu, Naresh Doni, Milliren, Carly E., Calfee, Carolyn S., Cairns, Charles B., Kraft, Monica, Baden, Lindsey R., Shaw, Albert C., Krammer, Florian, van Bakel, Harm, Esserman, Denise A., Liu, Shanshan, Sesma, Ana Fernandez, Simon, Viviana, Hafler, David A., Montgomery, Ruth R., Kleinstein, Steven H., Levy, Ofer, Bime, Chris, Haddad, Elias K., Erle, David J., Pulendran, Bali, Nadeau, Kari C., Davis, Mark M, Hough, Catherine L., Messer, William B., Higuita, Nelson I. Agudelo, Metcalf, Jordan P., Atkinson, Mark A., Brakenridge, Scott C., Corry, David, Kheradmand, Farrah, Ehrlich, Lauren I.R., Melamed, Esther, McComsey, Grace A., Sekaly, Rafick, Diray-Arce, Joann, Peters, Bjoern, Augustine, Alison D., Reed, Elaine F., McEnaney, Kerry, Barton, Brenda, Lentucci, Claudia, Saluvan, Mehmet, Chang, Ana C., Hoch, Annmarie, Albert, Marisa, Shaheen, Tanzia, Kho, Alvin T., Thomas, Sanya, Chen, Jing, Murphy, Maimouna D., Cooney, Mitchell, Presnell, Scott, Fragiadakis, Gabriela K., Patel, Ravi, Guan, Leying, Gygi, Jeremy, Pawar, Shrikant, Brito, Anderson, Khalil, Zain, Maguire, Cole, Fourati, Slim, Overton, James A., Vita, Randi, Westendorf, Kerstin, Salehi-Rad, Ramin, Leligdowicz, Aleksandra, Matthay, Michael A., Singer, Jonathan P., Kangelaris, Kirsten N., Hendrickson, Carolyn M., Krummel, Matthew F., Langelier, Charles R., Woodruff, Prescott G., Powell, Debra L., Kim, James N., Simmons, Brent, Goonewardene, I. Michael, Smith, Cecilia M., Martens, Mark, Mosier, Jarrod, Kimura, Hiroki, Sherman, Amy C., Walsh, Stephen R., Issa, Nicolas C., Dela Cruz, Charles, Farhadian, Shelli, Iwasaki, Akiko, Ko, Albert I., Chinthrajah, Sharon, Ahuja, Neera, Rogers, Angela J., Artandi, Maja, Siegel, Sarah A.R., Lu, Zhengchun, Drevets, Douglas A., Brown, Brent R., Anderson, Matthew L., Guirgis, Faheem W., Thyagarajan, Rama V., Rousseau, Justin F., Wylie, Dennis, Busch, Johanna, Gandhi, Saurin, Triplett, Todd A., Yendewa, George, Giddings, Olivia, Anderson, Evan J., Mehta, Aneesh K., Sevransky, Jonathan E., Khor, Bernard, Rahman, Adeeb, Stadlbauer, Daniel, Dutta, Jayeeta, Xie, Hui, Kim-Schulze, Seunghee, Gonzalez-Reiche, Ana Silvia, van de Guchte, Adriana, Farrugia, Keith, Khan, Zenab, Maecker, Holden T., Elashoff, David, Brook, Jenny, Ramires-Sanchez, Estefania, Llamas, Megan, Rivera, Adreanne, Perdomo, Claudia, Ward, Dawn C., Magyar, Clara E., Fulcher, Jennifer A., Abe-Jones, Yumiko, Asthana, Saurabh, Beagle, Alexander, Bhide, Sharvari, Carrillo, Sidney A., Chak, Suzanna, Ghale, Rajani, Gonzalez, Ana, Jauregui, Alejandra, Jones, Norman, Lea, Tasha, Lee, Deanna, Lota, Raphael, Milush, Jeff, Nguyen, Viet, Pierce, Logan, Prasad, Priya A., Rao, Arjun, Samad, Bushra, Shaw, Cole, Sigman, Austin, Sinha, Pratik, Ward, Alyssa, Willmore, Andrew, Zhan, Jenny, Rashid, Sadeed, Rodriguez, Nicklaus, Tang, Kevin, Altamirano, Luz Torres, Betancourt, Legna, Curiel, Cindy, Sutter, Nicole, Paz, Maria Tercero, Tietje-Ulrich, Gayelan, Leroux, Carolyn, Connors, Jennifer, Bernui, Mariana, Kutzler, Michel A., Edwards, Carolyn, Lee, Edward, Lin, Edward, Croen, Brett, Semenza, Nicholas C., Rogowski, Brandon, Melnyk, Nataliya, Woloszczuk, Kyra, Cusimano, Gina, Bell, Mathew R., Furukawa, Sara, McLin, Renee, Marrero, Pamela, Sheidy, Julie, Tegos, George P., Nagle, Crystal, Mege, Nathan, Ulring, Kristen, Seyfert-Margolis, Vicki, Conway, Michelle, Francisco, Dave, Molzahn, Allyson, Erickson, Heidi, Wilson, Connie Cathleen, Schunk, Ron, Sierra, Bianca, Hughes, Trina, Smolen, Kinga, Desjardins, Michael, van Haren, Simon, Mitre, Xhoi, Cauley, Jessica, Li, Xiaofang, Tong, Alexandra, Evans, Bethany, Montesano, Christina, Licona, Jose Humberto, Krauss, Jonathan, Chang, Jun Bai Park, Izaguirre, Natalie, Chaudhary, Omkar, Coppi, Andreas, Fournier, John, Mohanty, Subhasis, Muenker, M. Catherine, Nelson, Allison, Raddassi, Khadir, Rainone, Michael, Ruff, William E., Salahuddin, Syim, Schulz, Wade L., Vijayakumar, Pavithra, Wang, Haowei, Wunder Jr., Elsio, Young, H. Patrick, Zhao, Yujiao, Saksena, Miti, Altman, Deena, Kojic, Erna, Srivastava, Komal, Eaker, Lily Q., Bermúdez-González, Maria C., Beach, Katherine F., Sominsky, Levy A., Azad, Arman R., Carreño, Juan Manuel, Singh, Gagandeep, Raskin, Ariel, Tcheou, Johnstone, Bielak, Dominika, Kawabata, Hisaaki, Mulder, Lubbertus CF, Kleiner, Giulio, Lee, Alexandra S., Do, Evan Do, Fernandes, Andrea, Manohar, Monali, Hagan, Thomas, Blish, Catherine A., Din, Hena Naz, Roque, Jonasel, Yang, Samuel, Brunton, Amanda, Sullivan, Peter E., Strnad, Matthew, Lyski, Zoe L., Coulter, Felicity J., Booth, J. Leland, Sinko, Lauren A., Moldawer, Lyle L., Borresen, Brittany, Roth-Manning, Brittney, Song, Li-Zhen, Nelson, Ebony, Lewis-Smith, Megan, Smith, Jacob, Tipan, Pablo Guaman, Siles, Nadia, Bazzi, Sam, Geltman, Janelle, Hurley, Kerin, Gabriele, Gio, Sieg, Scott, Vaysman, Tatyana, Bristow, Laurel, Hussaini, Laila, Hellmeister, Kieffer, Samaha, Hady, Cheng, Andrew, Spainhour, Christine, Scherer, Erin M., Johnson, Brandi, Bechnak, Amer, Ciric, Caroline R., Hewitt, Lauren, Carter, Erin, Mcnair, Nina, Panganiban, Bernadine, Huerta, Christopher, Usher, Jacob, Ribeiro, Susan Pereira, Altman, Matthew C., Becker, Patrice M., Rouphael, Nadine, Bime, Christian, and Davis, Mark M.

Published
2022
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7. Durability of immune responses to mRNA booster vaccination against COVID-19

Author

Arunachalam, Prabhu S., Lai, Lilin, Samaha, Hady, Feng, Yupeng, Hu, Mengyun, Hui, Harold Sai-yin, Wali, Bushra, Ellis, Madison, Davis-Gardner, Meredith E., Huerta, Christopher, Bechnak, Kareem, Bechnak, Sarah, Lee, Matthew, Litvack, Matthew B., Losada, Cecilia, Grifoni, Alba, Sette, Alessandro, Zarnitsyna, Veronika I., Rouphael, Nadine, Suthar, Mehul S., and Pulendran, Bali

Subjects
Immune response -- Health aspects -- Physiological aspects, Health care industry, Comirnaty (Vaccine) -- Physiological aspects -- Comparative analysis, Spikevax (Vaccine) -- Comparative analysis -- Physiological aspects
Abstract

BACKGROUND. Maintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown. METHODS. We measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses. RESULTS. The booster (third immunization) dose at 6 to 10 months increased the half-life of the serum-neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months. CONCLUSION. The durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines., Introduction Recent studies have shown the declining efficacy of the Pfizer-BioNTech (BNT162b2) and Moderna (mRNA1273) mRNA vaccines after primary and booster vaccinations (1, 2). Although the booster vaccination (third dose) [...]

Published
2023
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8. Burden of Vaccine-Preventable Diseases in People Living with HIV.

Author

Samaha, Hady, Yigitkanli, Arda, Naji, Amal, Kazzi, Bahaa, Tanios, Ralph, Dib, Serena Maria, Ofotokun, Ighovwerha, and Rouphael, Nadine

Subjects
HIV-positive persons, VACCINATION status, VACCINE effectiveness, PUBLIC health, SEROCONVERSION
Abstract

Vaccine-preventable diseases (VPDs) pose a serious public health concern for people living with HIV (PLH). PLH experience a delayed and weakened response to many vaccines available, compared to the general population. Lower seroconversion rates, along with a decreased efficacy and durability of vaccines, increases the susceptibility of PLH to VPDs. Vaccination guidelines specifically targeting this population have been modified to overcome these challenges. However, vaccine uptake remains suboptimal due to multiple barriers, highlighting the need for further studies and the additional implementation of public health measures specifically tailored to PLH. [ABSTRACT FROM AUTHOR]

Published
2024
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9. AS03 adjuvant enhances the magnitude, persistence, and clonal breadth of memory B cell responses to a plant-based COVID-19 vaccine in humans.

Author

Grigoryan, Lilit, Feng, Yupeng, Bellusci, Lorenza, Lai, Lilin, Wali, Bushra, Ellis, Madison, Yuan, Meng, Arunachalam, Prabhu S., Hu, Mengyun, Kowli, Sangeeta, Gupta, Sheena, Maysel-Auslender, Sofia, Maecker, Holden T., Samaha, Hady, Rouphael, Nadine, Wilson, Ian A., Moreno, Alberto C., Suthar, Mehul S., Khurana, Surender, and Pillet, Stéphane

Subjects
IMMUNOLOGIC memory, COVID-19 pandemic, COVID-19 vaccines, VIRUS-like particles, MESSENGER RNA
Abstract

Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to the generation of antigen-specific B cell clones with distinct specificities or the maturation of memory B cell clones that produce broadly cross-reactive antibodies is unknown. Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination with either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted with AS03 (CoVLP+AS03), or a messenger RNA vaccination (mRNA-1273). CoVLP+AS03 enhanced the magnitude and durability of circulating antibodies and antigen-specific CD4+ T cell and memory B cell responses. Antigen-specific CD4+ T cells in the CoVLP+AS03 group at day 42 correlated with antigen-specific memory B cells at 6 months. CoVLP+AS03 induced memory B cell responses, which accumulated somatic hypermutations over 6 months, resulting in enhanced neutralization breadth of monoclonal antibodies. Furthermore, the fraction of broadly neutralizing antibodies encoded by memory B cells increased between day 42 and 6 months. These results indicate that AS03 enhances the antigenic breadth of B cell memory at the clonal level and induces progressive maturation of the B cell response. Editor's summary: Adjuvants are known to improve the magnitude, durability, and breadth of the immune response to vaccination, but how they modulate memory B cells is unclear. Grigoryan et al. analyzed immune responses in healthy individuals at multiple time points after two-dose vaccination with a plant-based SARS-CoV-2 vaccine (CoVLP) with or without adjuvant (AS03). AS03 adjuvant induced robust and more persistent RBD-specific memory B cells with increased neutralization breadth. This was due to AS03 promoting the selection of broadly neutralizing memory B cells, which accumulated SHMs over time. These findings highlight the role of adjuvants in enhancing memory B cell responses to vaccination. —Hannah Isles [ABSTRACT FROM AUTHOR]

Published
2024
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12. Bivalent and Monovalent SARS-CoV-2 Variant Vaccine Boosters Improve coverage of the known Antigenic Landscape: Results of the COVID-19 Variant Immunologic Landscape (COVAIL) Trial

Author

Branche, Angela, primary, Rouphael, Nadine, additional, Diemert, David, additional, Falsey, Ann, additional, Losada, Cecilia, additional, Baden, Lindsey (R), additional, Frey, Sharon, additional, Whitaker, Jennifer, additional, Little, Susan, additional, Anderson, Evan, additional, Walter, Emmanuel, additional, Novak, Richard, additional, Rupp, Richard, additional, Jackson, Lisa, additional, Babu, Tara, additional, Kottkamp, Angelica, additional, Luetkemeyer, Annie, additional, Immergluck, Lilly, additional, Presti, Rachel, additional, Backer, Martin, additional, Winokur, Patricia, additional, Mahgoub, Siham, additional, Goepfert, Paul, additional, Fusco, Dahlene, additional, Malkin, Elissa, additional, Bethony, Jeff, additional, Walsh, Edward, additional, Graciaa, Daniel, additional, Samaha, Hady, additional, Sherman, Amy, additional, Walsh, Stephen, additional, Abate, Getahun, additional, Oikonomopoulou, Zacharoula, additional, Sahly, Hana El, additional, Martin, Thomas, additional, Kamidani, Satoshi, additional, Smith, Michael, additional, Ladner, Benjamin, additional, Porterfield, Laura, additional, Dunstan, Maya, additional, Wald, Anna, additional, Davis, Tamia, additional, Atmar, Robert, additional, Mulligan, Mark, additional, Lyke, Kirsten, additional, Posavad, Christine, additional, Meagher, Megan, additional, Stephens, David, additional, Neuzil, Kathleen, additional, Abebe, Kuleni, additional, Hill, Heather, additional, Albert, Jim, additional, Telu, Kalyani, additional, Mu, Jinjian, additional, Lewis, Teri, additional, Giebeig, Lisa, additional, Eaton, Amanda, additional, Netzl, Antonia, additional, Wilks, Sam, additional, Tureli, Sina, additional, Makhene, Mamodikoe, additional, Crandon, Sonja, additional, Montefiori, David, additional, Makowski, Mat, additional, Smith, Derek, additional, Nayak, Seema, additional, Roberts, Paul, additional, and Beigel, John, additional

Published
2023
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13. Role of IgG glycans in severe COVID-19 inflammatory cytokine responses

Author

Scherer, Erin M., primary, Sherman, Jacob D., additional, Karmali, Vinit, additional, Kumar, Bhoj, additional, Simon, Trevor W., additional, Bechnak, Sarah, additional, Ciric, Caroline R., additional, Gray, Natalie, additional, Huerta, Christopher, additional, Hussaini, Laila, additional, Johnson, Brandi, additional, Lee, Matthew, additional, Panganiban, Bernadine, additional, Panjwani, Anusha, additional, Samaha, Hady, additional, Wang, Dongli, additional, Anderson, Evan J., additional, Azadi, Parastoo, additional, Collins, Matthew H., additional, Rostad, Christina A., additional, and Rouphael, Nadine, additional

Published
2023
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14. Heterologous versus homologous boosting regimens elicit qualitatively distinct, BA.5-cross reactive T cells in transplant recipients

Author

Thompson, Elizabeth A., primary, Ngecu, Wabathi, additional, Stoddart, Laila, additional, Johnston, T. Scott, additional, Chang, Amy, additional, Cascino, Katherine, additional, Alejo, Jennifer L., additional, Abedon, Aura T., additional, Samaha, Hady, additional, Rouphael, Nadine, additional, Tobian, Aaron A.R., additional, Segev, Dorry L., additional, Werbel, William A., additional, Karaba, Andrew H., additional, Blankson, Joel N., additional, and Cox, Andrea L., additional

Published
2023
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15. Durability of immune responses to the booster mRNA vaccination against COVID-19

Author

Arunachalam, Prabhu S, primary, Lai, Lilin, additional, Samaha, Hady, additional, Feng, Yupeng, additional, Hu, Mengyun, additional, Hui, Harold Sai-yin, additional, Wali, Bushra, additional, Ellis, Madison L., additional, Davis-Gardner, Meredith E., additional, Huerta, Christopher M., additional, Bechnak, Kareem, additional, Bechnak, Sarah, additional, Lee, Matthew, additional, Litvack, Matthew B., additional, Losada, Cecilia, additional, Grifoni, Alba, additional, Sette, Alessandro, additional, Zarnitsyna, Veronika I., additional, Rouphael, Nadine, additional, Suthar, Mehul S., additional, and Pulendran, Bali, additional

Published
2023
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16. Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster

Author

Davis-Gardner, Meredith E., primary, Lai, Lilin, additional, Wali, Bushra, additional, Samaha, Hady, additional, Solis, Daniel, additional, Lee, Matthew, additional, Porter-Morrison, Andrea, additional, Hentenaar, Ian T., additional, Yamamoto, Fumiko, additional, Godbole, Sucheta, additional, Liu, Yuan, additional, Douek, Daniel C., additional, Lee, Frances Eun-Hyung, additional, Rouphael, Nadine, additional, Moreno, Alberto, additional, Pinsky, Benjamin A., additional, and Suthar, Mehul S., additional

Published
2023
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17. Durability of immune responses to the booster mRNA vaccination against COVID-19

Author

Arunachalam, Prabhu S., primary, Lai, Lilin, additional, Samaha, Hady, additional, Feng, Yupeng, additional, Hu, Mengyun, additional, Hui, Harold Sai-yin, additional, Wali, Bushra, additional, Ellis, Madison, additional, Huerta, Christopher, additional, Bechnack, Kareem, additional, Bechnack, Sarah, additional, Lee, Matthew, additional, Litvack, Matthew, additional, Losada, Cecilia, additional, Grifoni, Alba, additional, Sette, Alessandro, additional, Zarnitsyna, Veronika I., additional, Rouphael, Nadine, additional, Suthar, Mehul S., additional, and Pulendran, Bali, additional

Published
2022
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18. mRNA bivalent booster enhances neutralization against BA.2.75.2 and BQ.1.1

Author

Davis-Gardner, Meredith E., primary, Lai, Lilin, additional, Wali, Bushra, additional, Samaha, Hady, additional, Solis, Daniel, additional, Lee, Matthew, additional, Porter-Morrison, Andrea, additional, Hentenaar, Ian Thomas, additional, Yamamoto, Fumiko, additional, Godbole, Sucheta, additional, Douek, Daniel C., additional, Lee, Frances Eun-Hyung, additional, Rouphael, Nadine, additional, Moreno, Alberto, additional, Pinsky, Benjamin A., additional, and Suthar, Mehul S., additional

Published
2022
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19. SARS-CoV-2 Variant Vaccine Boosters Trial: Preliminary Analyses

Author

Branche, Angela R., Rouphael, Nadine G., Diemert, David J., Falsey, Ann R., Losada, Cecilia, Baden, Lindsey R., Frey, Sharon E., Whitaker, Jennifer A., Little, Susan J., Anderson, Evan J., Walter, Emmanuel B., Novak, Richard M., Rupp, Richard, Jackson, Lisa A., Babu, Tara M., Kottkamp, Angelica C., Luetkemeyer, Anne F., Immergluck, Lilly C., Presti, Rachel M., Bäcker, Martín, Winokur, Patricia L., Mahgoub, Siham M., Goepfert, Paul A., Fusco, Dahlene N., Malkin, Elissa, Bethony, Jeffrey M., Walsh, Edward E., Graciaa, Daniel S., Samaha, Hady, Sherman, Amy C., Walsh, Stephen R., Abate, Getahun, Oikonomopoulou, Zacharoula, El Sahly, Hana M., Martin, Thomas C.S., Rostad, Christina A., Smith, Michael J., Ladner, Benjamin G., Porterfield, Laura, Dunstan, Maya, Wald, Anna, Davis, Tamia, Atmar, Robert L., Mulligan, Mark J., Lyke, Kirsten E., Posavad, Christine M., Meagher, Megan A., Stephens, David S., Neuzil, Kathleen M., Abebe, Kuleni, Hill, Heather, Albert, Jim, Lewis, Teri C., Giebeig, Lisa A., Eaton, Amanda, Netzl, Antonia, Wilks, Samuel H., Türeli, Sina, Makhene, Mamodikoe, Crandon, Sonja, Lee, Marina, Nayak, Seema U., Montefiori, David C., Makowski, Mat, Smith, Derek J., Roberts, Paul C., and Beigel, John H.

Subjects
Article
Abstract

BackgroundProtection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines.MethodsThis phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50µg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID50) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination.ResultsFrom March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907).ConclusionsHigher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines.Clinicaltrials.govNCT05289037

Published
2022

21. mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 omicron variant

Author

Edara, Venkata-Viswanadh, Manning, Kelly E., Ellis, Madison, Lai, Lilin, Moore, Kathryn M., Foster, Stephanie L., Floyd, Katharine, Davis-Gardner, Meredith E., Mantus, Grace, Nyhoff, Lindsay E., Bechnak, Sarah, Alaaeddine, Ghina, Naji, Amal, Samaha, Hady, Lee, Matthew, Bristow, Laurel, Gagne, Matthew, Roberts-Torres, Jesmine, Henry, Amy R., Godbole, Sucheta, Grakoui, Arash, Saxton, Marybeth, Piantadosi, Anne, Waggoner, Jesse J., Douek, Daniel C., Rouphael, Nadine, Wrammert, Jens, and Suthar, Mehul S.

Published
2022
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23. mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant

Author

Edara, Venkata-Viswanadh, primary, Manning, Kelly E., additional, Ellis, Madison, additional, Lai, Lilin, additional, Moore, Kathryn M., additional, Foster, Stephanie L., additional, Floyd, Katharine, additional, Davis-Gardner, Meredith E., additional, Mantus, Grace, additional, Nyhoff, Lindsay E., additional, Bechnak, Sarah, additional, Alaaeddine, Ghina, additional, Naji, Amal, additional, Samaha, Hady, additional, Lee, Matthew, additional, Bristow, Laurel, additional, Hussaini, Laila, additional, Ciric, Caroline Rose, additional, Nguyen, Phuong-Vi, additional, Gagne, Matthew, additional, Roberts-Torres, Jesmine, additional, Henry, Amy R., additional, Godbole, Sucheta, additional, Grakoui, Arash, additional, Sexton, Marybeth, additional, Piantadosi, Anne, additional, Waggoner, Jesse J., additional, Douek, Daniel C., additional, Anderson, Evan J., additional, Rouphael, Nadine, additional, Wrammert, Jens, additional, and Suthar, Mehul S., additional

Published
2021
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26. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients

Author

Diray-Arce, Joann, Fourati, Slim, Doni Jayavelu, Naresh, Patel, Ravi, Maguire, Cole, Chang, Ana C., Dandekar, Ravi, Qi, Jingjing, Lee, Brian H., van Zalm, Patrick, Schroeder, Andrew, Chen, Ernie, Konstorum, Anna, Brito, Anderson, Gygi, Jeremy P., Kho, Alvin, Chen, Jing, Pawar, Shrikant, Gonzalez-Reiche, Ana Silvia, Hoch, Annmarie, Milliren, Carly E., Overton, James A., Westendorf, Kerstin, Abraham, James, Adkisson, Michael, Albert, Marisa, Altamirano Torres, Luz, Alvarenga, Bonny, Anderson, Matthew L., Anderson, Evan J., Arnett, Azlann, Asashima, Hiromitsu, Atkinson, Mark A., Baden, Lindsey R., Barton, Brenda, Beach, Katherine, Beagle, Elizabeth, Becker, Patrice M., Bell, Matthew R., Bernui, Mariana, Bime, Chris, Boddapati Kumar, Arun, Booth, Leland J., Borresen, Brittney, Brakenridge, Scott C., Bristow, Laurel, Bryant, Robert, Calfee, Carolyn S., Carreño Manuel, Juan, Carrillo, Sidney, Chak, Suzanna, Chang, Iris, Connors, Jennifer, Conway, Michelle, Corry, David B., Cowan, David, Croen, Brett, Dela Cruz, Charles S., Cusimano, Gina, Eaker, Lily, Edwards, Carolyn, Ehrlich, Lauren I.R., Elashoff, David, Erickson, Heidi, Erle, David J., Farhadian, Shelli, Farrugia, Keith, Fatou, Benoit, Fernandes, Andrea, Fernandez-Sesma, Ana, Fragiadakis, Gabriela K., Furukawa, Sara, Geltman, Janelle N., Ghale, Rajani, González Carolina Bermúdez, Maria, Goonewardene, Michael I., Guerrero Sanchez, Estella, Guirgis, Faheem W., Hafler, David A., Hamilton, Sydney, Harris, Paul, Hayati Nemati, Arash, Hendrickson, Carolyn M., Higuita Agudelo, Nelson I., Hodder, Thomas, Holland, Steven M., Hough, Catherine L., Huerta, Christopher, Hurley, Kerin C., Hutton, Scott R., Iwasaki, Akiko, Jauregui, Alejandra, Jha, Meenakshi, Johnson, Brandi, Joyner, David, Kangelaris, Kirsten N., Kelly, Geoffrey, Khalil, Zain, Khan, Zenab, Kheradmand, Farrah, Kim, James N., Kimura, Hiroki, Ko, Albert I., Kohr, Bernard, Kraft, Monica, Krummel, Matthew, Kutzler, Michele F., Lasky-Su, Jessica, Lee, Serena, Lee, Deanna, Leipold, Michael, Lentucci, Claudia, Leroux, Carolyn, Lin, Edward, Liu, Shanshan, Love, Christina, Lu, Zhengchun, Maliskova, Lenka, Manning Roth, Brittany, Manohar, Monali, Martens, Mark, McComsey, Grace A., McEnaney, Kerry, McLin, Renee, Melamed, Esther, Melnyk, Nataliya, Mendez, Kevin, Messer, William B., Metcalf, Jordan P., Michelotti, Gregory, Mick, Eran, Mohanty, Subhasis, Mosier, Jarrod, Mulder, Lubbertus C.F., Murphy, Maimouna, Nadeau, Kari R.C., Nelson, Ebony, Nelson, Allison, Nguyen, Viet, Oberhaus, Jordan, Panganiban, Bernadine, Pellegrini, Kathryn L., Pickering, Harry C., Powell, Debra L., Presnell, Scott, Pulendran, Bali, Rahman, Adeeb H., Rashid Sadeed, Ahmad, Raskin, Ariel, Reed, Elaine F., Ribeiro Pereira, Susan, Rivera, Adreanne M., Rogers, Jacob E., Rogers, Angela, Rogowski, Brandon, Rooks, Rebecca, Rosenberg-Hasson, Yael, Rothman, Jessica, Rousseau, Justin F., Salehi-Rad, Ramin, Saluvan, Mehmet, Samaha, Hady, Schaenman, Joanna, Schunk, Ron, Semenza, Nicholas C., Sen, Subha, Sevransky, Jonathan, Seyfert-Margolis, Vicki, Shaheen, Tanzia, Shaw, Albert C., Sieg, Scott, Siegel, Sarah A.R., Sigal, Natalia, Siles, Nadia, Simmons, Brent, Simon, Viviana, Singh, Gagandeep, Sinko, Lauren, Smith, Cecilia M., Smolen, Kinga K., Song, Li-Zhen, Srivastava, Komal, Sullivan, Peter, Syphurs, Caitlin, Tcheou, Johnstone, Tegos, George P., Tharp, Greg K., Tong Ally, Alexandra, Tsitsiklis, Alexandra, Ungaro, Ricardo F., Vaysman, Tatyana, Viode, Arthur, Vita, Randi, Wang, Xiaomei, Ward, Alyssa, Ward, Dawn C., Willmore, Andrew, Woloszczuk, Kyra, Wong, Kari, Woodruff, Prescott G., Xu, Leqi, van Haren, Simon, van de Guchte, Adriana, Zhao, Yujiao, Cairns, Charles B., Rouphael, Nadine, Bosinger, Steven E., Kim-Schulze, Seunghee, Krammer, Florian, Rosen, Lindsey, Grubaugh, Nathan D., van Bakel, Harm, Wilson, Michael, Rajan, Jayant, Steen, Hanno, Eckalbar, Walter, Cotsapas, Chris, Langelier, Charles R., Levy, Ofer, Altman, Matthew C., Maecker, Holden, Montgomery, Ruth R., Haddad, Elias K., Sekaly, Rafick P., Esserman, Denise, Ozonoff, Al, Becker, Patrice M., Augustine, Alison D., Guan, Leying, Peters, Bjoern, and Kleinstein, Steven H.

Abstract

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1–3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.

Published
2023
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27. Heterologous versus homologous boosting elicits qualitatively distinct, BA.5-cross-reactive T cells in transplant recipients.

Author

Thompson EA, Ngecu W, Stoddart L, Johnston TS, Chang A, Cascino K, Alejo JL, Abedon AT, Samaha H, Rouphael N, Tobian AA, Segev DL, Werbel WA, Karaba AH, Blankson JN, and Cox AL

Subjects
Humans, Ad26COVS1, BNT162 Vaccine, COVID-19 Vaccines, Prospective Studies, SARS-CoV-2, Antibodies, Neutralizing, Immunoglobulin G, Transplant Recipients, COVID-19 prevention & control
Abstract

BackgroundThe SARS-CoV-2 Omicron BA.5 subvariant escapes vaccination-induced neutralizing antibodies because of mutations in the spike (S) protein. Solid organ transplant recipients (SOTRs) develop high COVID-19 morbidity and poor Omicron variant recognition after COVID-19 vaccination. T cell responses may provide a second line of defense. Therefore, understanding which vaccine regimens induce robust, conserved T cell responses is critical.MethodsWe evaluated anti-S IgG titers, subvariant pseudo-neutralization, and S-specific CD4+ and CD8+ T cell responses from SOTRs in a national, prospective, observational trial (n = 75). Participants were selected if they received 3 doses of mRNA (homologous boosting) or 2 doses of mRNA followed by Ad26.COV2.S (heterologous boosting).ResultsHomologous boosting with 3 mRNA doses induced the highest anti-S IgG titers. However, antibodies induced by both vaccine regimens demonstrated lower pseudo-neutralization against BA.5 compared with the ancestral strain. In contrast, vaccine-induced S-specific T cells maintained cross-reactivity against BA.5 compared with ancestral recognition. Homologous boosting induced higher frequencies of activated polyfunctional CD4+ T cell responses, with polyfunctional IL-21+ peripheral T follicular helper cells increased in mRNA-1273 compared with BNT162b2. IL-21+ cells correlated with antibody titers. Heterologous boosting with Ad26.COV2.S did not increase CD8+ responses compared to homologous boosting.ConclusionBoosting with the ancestral strain can induce cross-reactive T cell responses against emerging variants in SOTRs, but alternative vaccine strategies are required to induce robust CD8+ T cell responses.FundingBen-Dov Family; NIH National Institute of Allergy and Infectious Diseases (NIAID) K24AI144954, NIAID K08AI156021, NIAID K23AI157893, NIAID U01AI138897, National Institute of Diabetes and Digestive and Kidney Diseases T32DK007713, and National Cancer Institute 1U54CA260492; Johns Hopkins Vice Dean of Research Support for COVID-19 Research in Immunopathogenesis; and Emory COVID-19 research repository.

Published
2023
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28. Bivalent and Monovalent SARS-CoV-2 Variant Vaccine Boosters Improve coverage of the known Antigenic Landscape: Results of the COVID-19 Variant Immunologic Landscape (COVAIL) Trial.

Author

Branche A, Rouphael N, Diemert D, Falsey A, Losada C, Baden LR, Frey S, Whitaker J, Little S, Anderson E, Walter E, Novak R, Rupp R, Jackson L, Babu T, Kottkamp A, Luetkemeyer A, Immergluck L, Presti R, Backer M, Winokur P, Mahgoub S, Goepfert P, Fusco D, Malkin E, Bethony J, Walsh E, Graciaa D, Samaha H, Sherman A, Walsh S, Abate G, Oikonomopoulou Z, El Sahly H, Martin T, Kamidani S, Smith M, Ladner B, Porterfield L, Dunstan M, Wald A, Davis T, Atmar R, Mulligan M, Lyke K, Posavad C, Meagher M, Stephens D, Neuzil K, Abebe K, Hill H, Albert J, Telu K, Mu J, Lewis T, Giebeig L, Eaton A, Netzl A, Wilks S, Tureli S, Makhene M, Crandon S, Montefiori D, Makowski M, Smith D, Nayak S, Roberts P, and Beigel J

Abstract

Vaccine protection against COVID-19 wanes over time and has been impacted by the emergence of new variants with increasing escape of neutralization. The COVID-19 Variant Immunologic Landscape (COVAIL) randomized clinical trial (clinicaltrials.gov NCT05289037) compares the breadth, magnitude and durability of antibody responses induced by a second COVID-19 vaccine boost with mRNA (Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2), or adjuvanted recombinant protein (Sanofi CoV2 preS DTM-AS03) monovalent or bivalent vaccine candidates targeting ancestral and variant SARS-CoV-2 spike antigens (Beta, Delta and Omicron BA.1). We found that boosting with a variant strain is not associated with loss in neutralization against the ancestral strain. However, while variant vaccines compared to the prototype/wildtype vaccines demonstrated higher neutralizing activity against Omicron BA.1 and BA.4/5 subvariants for up to 3 months after vaccination, neutralizing activity was lower for more recent Omicron subvariants. Our study, incorporating both antigenic distances and serologic landscapes, can provide a framework for objectively guiding decisions for future vaccine updates.

Published
2023
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29. Durability of immune responses to the booster mRNA vaccination against COVID-19.

Author

Arunachalam PS, Lai L, Samaha H, Feng Y, Hu M, Hui HS, Wali B, Ellis M, Huerta C, Bechnack K, Bechnack S, Lee M, Litvack M, Losada C, Grifoni A, Sette A, Zarnitsyna VI, Rouphael N, Suthar MS, and Pulendran B

Abstract

Waning immunity to vaccination represents a major challenge in vaccinology. Whether booster vaccination improves the durability of immune responses is unknown. Here we show, using a cohort of 55 adult vaccinees who received the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine against SARS-CoV-2, that a booster (i.e., 3 rd immunization) dose at 6 - 10 months increased the half-life of serum neutralizing antibody (nAb) titers to 76 days from 56 - 66 days estimated after the primary two-dose vaccination series. A second booster dose (i.e., 4 th immunization) more than a year after the primary vaccination increased the half-life further to 88 days. However, despite this modestly improved durability in nAb responses against the Wuhan strain, there was a loss in neutralization capacity against Omicron subvariants, especially the recently emerged variants, BA.2.75.2 and BQ.1.1 (35 and 50-fold drop in titers respectively, relative to the ancestral (WA.1) strain. While only 55 â€" 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (3 rd dose), the response declined to below the detection limit in almost all individuals by 6 months. Notably, even against BA.1 and BA.5, the titers declined rapidly in a third of the vaccinees and were below the detection limit at 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months. Collectively, our data show that the durability of immune responses improves following subsequent booster immunizations; however, the emergence of immune evasive variants reduces the effectiveness of booster doses in preventing infection.

Published
2022
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30. mRNA bivalent booster enhances neutralization against BA.2.75.2 and BQ.1.1.

Author

Davis-Gardner ME, Lai L, Wali B, Samaha H, Solis D, Lee M, Porter-Morrison A, Hentenaar IT, Yamamoto F, Godbole S, Douek DC, Lee FE, Rouphael N, Moreno A, Pinsky BA, and Suthar MS

Abstract

The emergence of the highly divergent SARS-CoV-2 Omicron variant has jeopardized the efficacy of vaccines based on the ancestral spike. The bivalent COVID-19 mRNA booster vaccine within the United States is comprised of the ancestral and the Omicron BA.5 spike. Since its approval and distribution, additional Omicron subvariants have been identified with key mutations within the spike protein receptor binding domain that are predicted to escape vaccine sera. Of particular concern is the R346T mutation which has arisen in multiple subvariants, including BA.2.75.2 and BQ.1.1. Using a live virus neutralization assay, we evaluated serum samples from individuals who had received either one or two monovalent boosters or the bivalent booster to determine neutralizing activity against wild-type (WA1/2020) virus and Omicron subvariants BA.1, BA.5, BA.2.75.2, and BQ.1.1. In the one monovalent booster cohort, relative to WA1/2020, we observed a reduction in neutralization titers of 9-15-fold against BA.1 and BA.5 and 28-39-fold against BA.2.75.2 and BQ.1.1. In the BA.5-containing bivalent booster cohort, the neutralizing activity improved against all the Omicron subvariants. Relative to WA1/2020, we observed a reduction in neutralization titers of 3.7- and 4-fold against BA.1 and BA.5, respectively, and 11.5- and 21-fold against BA.2.75.2 and BQ.1.1, respectively. These data suggest that the bivalent mRNA booster vaccine broadens humoral immunity against the Omicron subvariants.

Published
2022
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31. SARS-CoV-2 Variant Vaccine Boosters Trial: Preliminary Analyses.

Author

Branche AR, Rouphael NG, Diemert DJ, Falsey AR, Losada C, Baden LR, Frey SE, Whitaker JA, Little SJ, Anderson EJ, Walter EB, Novak RM, Rupp R, Jackson LA, Babu TM, Kottkamp AC, Luetkemeyer AF, Immergluck LC, Presti RM, Bäcker M, Winokur PL, Mahgoub SM, Goepfert PA, Fusco DN, Malkin E, Bethony JM, Walsh EE, Graciaa DS, Samaha H, Sherman AC, Walsh SR, Abate G, Oikonomopoulou Z, El Sahly HM, Martin TCS, Rostad CA, Smith MJ, Ladner BG, Porterfield L, Dunstan M, Wald A, Davis T, Atmar RL, Mulligan MJ, Lyke KE, Posavad CM, Meagher MA, Stephens DS, Neuzil KM, Abebe K, Hill H, Albert J, Lewis TC, Giebeig LA, Eaton A, Netzl A, Wilks SH, Türeli S, Makhene M, Crandon S, Lee M, Nayak SU, Montefiori DC, Makowski M, Smith DJ, Roberts PC, and Beigel JH

Abstract

Background: Protection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines., Methods: This phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50µg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID 50 ) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination., Results: From March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907)., Conclusions: Higher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines., Clinicaltrialsgov: NCT05289037.

Published
2022
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32. mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant.

Author

Edara VV, Manning KE, Ellis M, Lai L, Moore KM, Foster SL, Floyd K, Davis-Gardner ME, Mantus G, Nyhoff LE, Bechnak S, Alaaeddine G, Naji A, Samaha H, Lee M, Bristow L, Hussaini L, Ciric CR, Nguyen PV, Gagne M, Roberts-Torres J, Henry AR, Godbole S, Grakoui A, Sexton M, Piantadosi A, Waggoner JJ, Douek DC, Anderson EJ, Rouphael N, Wrammert J, and Suthar MS

Abstract

The BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines generate potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the global emergence of SARS-CoV-2 variants with mutations in the spike protein, the principal antigenic target of these vaccines, has raised concerns over the neutralizing activity of vaccine-induced antibody responses. The Omicron variant, which emerged in November 2021, consists of over 30 mutations within the spike protein. Here, we used an authentic live virus neutralization assay to examine the neutralizing activity of the SARS-CoV-2 Omicron variant against mRNA vaccine-induced antibody responses. Following the 2nd dose, we observed a 30-fold reduction in neutralizing activity against the omicron variant. Through six months after the 2nd dose, none of the sera from naïve vaccinated subjects showed neutralizing activity against the Omicron variant. In contrast, recovered vaccinated individuals showed a 22-fold reduction with more than half of the subjects retaining neutralizing antibody responses. Following a booster shot (3rd dose), we observed a 14-fold reduction in neutralizing activity against the omicron variant and over 90% of boosted subjects showed neutralizing activity against the omicron variant. These findings show that a 3rd dose is required to provide robust neutralizing antibody responses against the Omicron variant.

Published
2021
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