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1. The Impact of COVID-19, Mental Health Distress, and School-Based Sociocultural Protective Factors among Elementary-Aged Children and Their Caregivers

Author

Goodwin, Aijah K. B., Roberson, Anthony J., Watson, Ar'Reon, Chen, Grace L., and Long, Anna C. J.

Abstract

Given the individual and systemic stress endured by children and families during the COVID-19 pandemic, research examining culturally responsive school experiences and supports to enhance resilience is critical. This study examined the relationship between caregivers' perceptions of COVID-19 impact, mental health distress among children and caregivers, and school-based sociocultural protective factors, including culturally responsive practices in schools and the relationships between teachers and caregivers, concurrently and longitudinally. Data were collected from caregivers of elementary-aged children at two-time points from March to April 2020 (N = 174) and one year later in 2021 (N = 114). Regression analyses revealed that COVID-19 impact positively predicted and parent-teacher joining negatively predicted mental health concerns among children and families, concurrently and longitudinally. Furthermore, there was a positive relationship between caregivers' perceptions of teachers' social awareness and justice practices and mental health symptoms for children in 2020. Parent-teacher joining longitudinally moderated the relationship between COVID-19 impact and caregivers' mental health concerns. This study provides implications regarding sociocultural resilience factors that should be considered in schools amidst the COVID-19 pandemic.

Published
2023
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4. Mental Health, Well-Being, and Help-Seeking in Schools among Black Adolescents: The Role of Discrimination in High-Achieving Academic Settings

Author

Goodwin, Aijah K. B., Chen, Grace L., and Long, Anna C. J.

Abstract

The underrepresentation of Black youth in high-achieving academic settings places significant importance on examining their daily experiences. This study investigated the relationship between school discrimination, well-being in academic settings, the risk for anxiety and depression, and school mental health help-seeking intentions. Participants included 110 Black high school students (66% women; mean age = 15.67) attending a special-admissions public school who participated in their school universal mental health screening. Black high school students in this high achieving context experienced few occurrences of school discrimination, yet these experiences still significantly impacted their internalizing severity. The mediation analyses revealed that experiences of discrimination predicted lower levels of academic efficacy and school connectedness, which predicted higher levels of internalizing symptoms. Experiences of discrimination were not related to mental health help-seeking at school. However, Black youth's intentions to seek mental health services at school were low, regardless of discriminatory experiences, as evidenced by the percentage of universal screening dissent and their self-reported plans to seek support. The findings highlight the need to consider Black adolescents' experiences in high achieving schools when engaged in universal mental health screening and individual and school-wide mental health prevention efforts.

Published
2021
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5. Safety and immunogenicity of a trivalent virus-like particle vaccine against western, eastern, and Venezuelan equine encephalitis viruses: a phase 1, open-label, dose-escalation, randomised clinical trial

Author

Butler, Ellie, Winter, Jean, Xu, Jianguo, Sherman, Amy, Kelley, Colleen, Fredrick, Rameses, Rouphael, Nadine, Phadke, Varun, Whitney, Cynthia, Alvarez, Alicarmen, Dennis, Renata, Fineman, Rebecca, Lankford-Turner, Pamela, Yi, Sha, Lai, Lilin, Burch, Gena, Gupta, Shanker, Berkowitz, Nina, Carter, Cristina, Beck, Allison, Larkin, Brenda, Taylor, Stephanie, Alger, Mandy, Bahorich, Jessica, Lynch Chamberlain, Amy, Chang, Ya-chen, Chaudhuri, Rajoshi, Cooper, Jonathan, Demirji, Jacob, Yang, Fan, Fernald, Alissa, Gollapudi, Deepika, Holland-Linn, Janel, Kueltzo, Lisa, Lee, James, Liu, Jie, Liu, Xun, Mowery, Rachel, O'Connell, Sarah, Rosales-Zavala, Erwin, Sands, Jason, Wang, Xin, Weng, Shaojie, Witter, Sara, Coates, Emily E, Edupuganti, Srilatha, Chen, Grace L, Happe, Myra, Strom, Larisa, Widge, Alicia, Florez, Maria Burgos, Cox, Josephine H, Gordon, Ingelise, Plummer, Sarah, Ola, Abidemi, Yamshchikov, Galina, Andrews, Charla, Curate-Ingram, Sharon, Morgan, Patricia, Nagar, Shashi, Collins, Matthew H, Bray, Amy, Nguyen, Thuy, Stein, Judy, Case, Christopher L, Kaltovich, Florence, Wycuff, Diane, Liang, C Jason, Carlton, Kevin, Vazquez, Sandra, Mascola, John R, and Ledgerwood, Julie E

Published
2022
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6. Safety and Immunogenicity of an mRNA-Based RSV Vaccine Including a 12-Month Booster in a Phase 1 Clinical Trial in Healthy Older Adults.

Author

Shaw, Christine A, Essink, Brandon, Harper, Charles, Mithani, Runa, Kapoor, Archana, Dhar, Rakesh, Wilson, Lauren, Guo, Ruiting, Panozzo, Catherine A, Wilson, Eleanor, Simorellis, Alana K, Reuter, Caroline, Stoszek, Sonia K, Chen, Grace L, Das, Rituparna, and Goswami, Jaya

Subjects
CLINICAL trial registries, RESPIRATORY syncytial virus infections, RESPIRATORY syncytial virus infection vaccines, ANTIBODY titer, RESPIRATORY syncytial virus
Abstract

Background An mRNA-based respiratory syncytial virus (RSV) vaccine, mRNA-1345, is under clinical investigation to address RSV disease burden in older adults. Methods Based on a randomized, observer-blind, placebo-controlled design, this phase 1 dose-ranging study evaluated the safety, reactogenicity, and immunogenicity of mRNA-1345 in adults aged 65 to 79 years. Participants were randomized to receive 1 dose of mRNA-1345 (12.5, 25, 50, 100, or 200 µg) or placebo and matched mRNA-1345 booster or placebo at 12 months. Results Overall, 298 participants received the first injection and 247 received the 12-month booster injection. mRNA-1345 was generally well tolerated after both injections, with the most frequently reported solicited adverse reactions being injection site pain, fatigue, headache, arthralgia, and myalgia. Reactogenicity was higher after the booster injection but with severity, time to onset, and duration similar to the first injection. A single mRNA-1345 injection boosted RSV-A and RSV-B neutralizing antibody titers and prefusion F binding antibody (preF bAb) concentrations at 1 month (geometric mean fold rises: RSV-A, 10.2–16.5; RSV-B, 5.3–12.5; preF bAb, 7.2–12.1). RSV antibody levels remained above baseline through 12 months, indicating immune persistence. A 12-month booster injection also increased RSV-A and RSV-B neutralizing antibody titers and preF bAb concentrations; titers after booster injection were numerically lower than those after the first dose, with overlapping 95% CIs. Conclusions mRNA-1345 was well tolerated and immunogenic following a single injection and a 12-month booster. Clinical Trials Registration NCT04528719 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Published
2024
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7. Safety, Tolerability, and Immunogenicity of an mRNA-Based Respiratory Syncytial Virus Vaccine in Healthy Young Adults in a Phase 1 Clinical Trial.

Author

Shaw, Christine A, Mithani, Runa, Kapoor, Archana, Dhar, Rakesh, Wilson, Lauren, Asmar, Laila El, Schnyder-Ghamloush, Sabine, Schaefers, Kristi, August, Allison, Stoszek, Sonia K, and Chen, Grace L

Subjects
CLINICAL trial registries, RESPIRATORY syncytial virus, RESPIRATORY syncytial virus infection vaccines, YOUNG adults, ANTIBODY titer, AUJESZKY'S disease virus
Abstract

Background Respiratory syncytial virus (RSV) presents a global health concern. A lipid nanoparticle–encapsulated mRNA-based RSV vaccine (mRNA-1345) that encodes the membrane-anchored RSV prefusion–stabilized F glycoprotein is under clinical investigation. Methods This phase 1 dose escalation study was based on a randomized, observer-blind, placebo-controlled design, and it assessed the safety and immunogenicity of mRNA-1345 in healthy adults aged 18 to 49 years. Participants were randomized to receive 1 dose of mRNA-1345 (50, 100, or 200 µg) or placebo or 3 doses of mRNA-1345 (100 µg) or placebo 56 days apart. Results mRNA-1345 was well tolerated at all dose levels. The most common solicited adverse reactions were pain, headache, fatigue, myalgia, or chills, which were all generally mild to moderate. At 1 month postinjection, a single injection of mRNA-1345 boosted RSV neutralizing antibody titers (geometric mean fold rise: RSV-A, 20.0–23.5; RSV-B, 11.7–16.0) and RSV prefusion binding antibody concentrations (geometric mean fold rise, 16.1–21.8), with no apparent dose response. Antibody levels remained above baseline through 6 months. Sequential doses of 100 µg were well tolerated but did not further boost antibody levels. Conclusions A single mRNA-1345 injection demonstrated an acceptable safety profile in younger adults and induced a durable neutralizing antibody response, supporting its continued development. Clinical Trials Registration ClinicalTrials.gov NCT04528719. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial

Author

Houser, Katherine V., Chen, Grace L., Carter, Cristina, Crank, Michelle C., Nguyen, Thuy A., Burgos Florez, Maria Claudia, Berkowitz, Nina M., Mendoza, Floreliz, Hendel, Cynthia Starr, Gordon, Ingelise J., Coates, Emily E., Vazquez, Sandra, Stein, Judy, Case, Christopher L., Lawlor, Heather, Carlton, Kevin, Gaudinski, Martin R., Strom, Larisa, Hofstetter, Amelia R., Liang, C. Jason, Narpala, Sandeep, Hatcher, Christian, Gillespie, Rebecca A., Creanga, Adrian, Kanekiyo, Masaru, Raab, Julie E., Andrews, Sarah F., Zhang, Yi, Yang, Eun Sung, Wang, Lingshu, Leung, Kwanyee, Kong, Wing-Pui, Freyn, Alec W., Nachbagauer, Raffael, Palese, Peter, Bailer, Robert T., McDermott, Adrian B., Koup, Richard A., Gall, Jason G., Arnold, Frank, Mascola, John R., Graham, Barney S., and Ledgerwood, Julie E.

Published
2022
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9. A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination

Author

Andrews, Sarah F., Raab, Julie E., Gorman, Jason, Gillespie, Rebecca A., Cheung, Crystal S. F., Rawi, Reda, Cominsky, Lauren Y., Boyington, Jeffrey C., Creanga, Adrian, Shen, Chen-Hsiang, Harris, Darcy R., Olia, Adam S., Nazzari, Alexandra F., Zhou, Tongqing, Houser, Katherine V., Chen, Grace L., Mascola, John R., Graham, Barney S., Kanekiyo, Masaru, Ledgerwood, Julie E., Kwong, Peter D., and McDermott, Adrian B.

Published
2022
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11. Safety, Tolerability and Immunogenicity of a mRNA-based RSV Vaccine in Healthy Young Adults in a Phase 1 Clinical Trial

Author

Shaw, Christine A, primary, Mithani, Runa, additional, Kapoor, Archana, additional, Dhar, Rakesh, additional, Wilson, Lauren, additional, El Asmar, Laila, additional, Schnyder-Ghamloush, Sabine, additional, Schaefers, Kristi, additional, August, Allison, additional, Stoszek, Sonia K, additional, and Chen, Grace L, additional

Published
2024
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12. Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults

Author

Wilson, Eleanor, primary, Goswami, Jaya, additional, Baqui, Abdullah H., additional, Doreski, Pablo A., additional, Perez-Marc, Gonzalo, additional, Zaman, Khalequ, additional, Monroy, Jorge, additional, Duncan, Christopher J.A., additional, Ujiie, Mugen, additional, Rämet, Mika, additional, Pérez-Breva, Lina, additional, Falsey, Ann R., additional, Walsh, Edward E., additional, Dhar, Rakesh, additional, Wilson, Lauren, additional, Du, Jiejun, additional, Ghaswalla, Parinaz, additional, Kapoor, Archana, additional, Lan, Lan, additional, Mehta, Shraddha, additional, Mithani, Runa, additional, Panozzo, Catherine A., additional, Simorellis, Alana K., additional, Kuter, Barbara J., additional, Schödel, Florian, additional, Huang, Wenmei, additional, Reuter, Caroline, additional, Slobod, Karen, additional, Stoszek, Sonia K., additional, Shaw, Christine A., additional, Miller, Jacqueline M., additional, Das, Rituparna, additional, and Chen, Grace L., additional

Published
2023
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13. Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial

Author

Mendoza, Floreliz, Novik, Laura, Zephir, Kathy, Whalen, William, Larkin, Brenda, Saunders, Jamie, Cunningham, Jennifer, Levinson, Carol, Wang, Xiaolin, Plummer, Sarah, Victorino, Milalynn, Ola, Abidemi, Boyd, Catina, Jayasinghe, Nilusha, Apte, Preeti, Cartagena, Cora Trelles, Hicks, Renunda, Williams, Pernell, Vasilenko, Olga, Yamshchikov, Galina, Florez, Maria Burgos, Pittman, Iris, Gama, Lucio, Casazza, Joseph, DeCederfelt, Hope, Cheng, KC, Stein, Judy, Gaudinski, Martin R, Houser, Katherine V, Doria-Rose, Nicole A, Chen, Grace L, Rothwell, Ro Shauna S, Berkowitz, Nina, Costner, Pamela, Holman, LaSonji A, Gordon, Ingelise J, Hendel, Cynthia S, Kaltovich, Florence, Conan-Cibotti, Michelle, Gomez Lorenzo, Margarita, Carter, Cristina, Sitar, Sandra, Carlton, Kevin, Gall, Jason, Laurencot, Carolyn, Lin, Bob C, Bailer, Robert T, McDermott, Adrian B, Ko, Sung-Youl, Pegu, Amarendra, Kwon, Young D, Kwong, Peter D, Namboodiri, Aryan M, Pandey, Janardan P, Schwartz, Richard, Arnold, Frank, Hu, Zonghui, Zhang, Lily, Huang, Yunda, Koup, Richard A, Capparelli, Edmund V, Graham, Barney S, Mascola, John R, and Ledgerwood, Julie E

Published
2019
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14. 2655. Phase 1 Safety and Immunogenicity Results of Two Investigational mRNA Vaccines, mRNA-1345, a Respiratory Syncytial Virus Vaccine, and mRNA-1653, a Human Metapneumovirus and Parainfluenza Virus Type 3 Combination Vaccine in Seropositive Young Children

Author

Snape, Matthew D, primary, Ghamloush, Sabine Schnyder, additional, Chen, Grace L, additional, Dhar, Rakesh, additional, Mithani, Runa, additional, Righi, Vinicius, additional, Morsy, Louie, additional, Kapoor, Archana, additional, Girard, Bethany, additional, Asmar, Laila El, additional, and Shaw, Christine A, additional

Published
2023
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16. Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials

Author

Plummer, Sarah, Costner, Pamela, Zephir, Kathryn, Casazza, Joseph, Ola, Abidemi, Victorino, Milalynn, Levinson, Carol, Whalen, William, Wang, Xiaolin, Cunningham, Jennifer, Vasilenko, Olga, Burgos Florez, Maria, Hickman, Somia, Pittman, Iris, Le, Lam, Larkin, Brenda, Andrews, Charla, Apte, Preeti, Hicks, Renunda, Trelles Cartagena, Cora, Williams, Pernell, Boyd, Catina R, Conan-Cibotti, Michelle, Stein, Judy, Kaltovich, Florence, DeCederfelt, Hope, McAdams, Stacey, Renehan, Phyllis, Chen, Wilbur, Greenberg, Nancy, Wymer, Nancy, Wadsworth, Linda, Billington, Melissa, Robinson, Toni, Boyce, Colleen, Pa'ahana Brown, Faith, Chrisley, Lisa, Kwon, Alyson, Patel, Prashant, Kominou, Panagoita, Dorsey, Brenda, Eddington, Staci, Telscher, Shinyi, Lee, Myoughee, Mosely, Regina, Ross, April, Ford, Geoffrey, Domjahn, Briyana, Xu, Jianguo, Beck, Allison, Fineman, Rebecca, Heeke, Shiela, Winter, Jean, Nagar, Shashi, Kelley, Colleen, Mulligan, Mark, Gaudinski, Martin R, Houser, Katherine V, Morabito, Kaitlyn M, Hu, Zonghui, Yamshchikov, Galina, Rothwell, Ro Shauna, Berkowitz, Nina, Mendoza, Floreliz, Saunders, Jamie G, Novik, Laura, Hendel, Cynthia S, Holman, LaSonji A, Gordon, Ingelise J, Cox, Josephine H, Edupuganti, Srilatha, McArthur, Monica A, Rouphael, Nadine G, Lyke, Kirsten E, Cummings, Ginny E, Sitar, Sandra, Bailer, Robert T, Foreman, Bryant M, Burgomaster, Katherine, Pelc, Rebecca S, Gordon, David N, DeMaso, Christina R, Dowd, Kimberly A, Laurencot, Carolyn, Schwartz, Richard M, Mascola, John R, Graham, Barney S, Pierson, Theodore C, Ledgerwood, Julie E, and Chen, Grace L

Published
2018
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17. Identifying Gaps in Respiratory Syncytial Virus Disease Epidemiology in the United States Prior to the Introduction of Vaccines

Author

Kim, Lindsay, Rha, Brian, Abramson, Jon S., Anderson, Larry J., Byington, Carrie L., Chen, Grace L., DeVincenzo, John, Edwards, Kathryn M., Englund, Janet A., Falsey, Ann R., Griffin, Marie R., Karron, Ruth A., Martin, Karen G., Meissner, H. Cody, Munoz, Flor M., Pavia, Andrew T., Piedra, Pedro A., Schaffner, William, Simões, Eric A. F., Singleton, Rosalyn, Talbot, H. Keipp, Walsh, Edward E., Zucker, Jane R., and Gerber, Susan I.

Published
2017

18. Immune memory shapes human polyclonal antibody responses to H2N2 vaccination

Author

Yang, Yuhe R., primary, Han, Julianna, additional, Perrett, Hailee R., additional, Richey, Sara T., additional, Jackson, Abigail M., additional, Rodriguez, Alesandra J., additional, Gillespie, Rebecca A., additional, O’Connell, Sarah, additional, Raab, Julie E., additional, Cominsky, Lauren Y., additional, Chopde, Ankita, additional, Kanekiyo, Masaru, additional, Houser, Katherine V., additional, Chen, Grace L., additional, McDermott, Adrian B., additional, Andrews, Sarah F., additional, and Ward, Andrew B., additional

Published
2023
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19. An influenza H1 hemagglutinin stem-only immunogen elicits a broadly cross-reactive B cell response in humans

Author

Andrews, Sarah F., primary, Cominsky, Lauren Y., additional, Shimberg, Geoffrey D., additional, Gillespie, Rebecca A., additional, Gorman, Jason, additional, Raab, Julie E., additional, Brand, Joshua, additional, Creanga, Adrian, additional, Gajjala, Suprabhath R., additional, Narpala, Sandeep, additional, Cheung, Crystal S. F., additional, Harris, Darcy R., additional, Zhou, Tongqing, additional, Gordon, Ingelise, additional, Holman, LaSonji, additional, Mendoza, Floreliz, additional, Houser, Katherine V., additional, Chen, Grace L., additional, Mascola, John R., additional, Graham, Barney S., additional, Kwong, Peter D., additional, Widge, Alicia, additional, Dropulic, Lesia K., additional, Ledgerwood, Julie E., additional, Kanekiyo, Masaru, additional, and McDermott, Adrian B., additional

Published
2023
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20. A prefusion-stabilized RSV F subunit vaccine elicits B cell responses with greater breadth and potency than a postfusion F vaccine

Author

Chang, Lauren A., primary, Phung, Emily, additional, Crank, Michelle C., additional, Morabito, Kaitlyn M., additional, Villafana, Tonya, additional, Dubovsky, Filip, additional, Falloon, Judith, additional, Esser, Mark T., additional, Lin, Bob C., additional, Chen, Grace L., additional, Graham, Barney S., additional, and Ruckwardt, Tracy J., additional

Published
2022
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24. Safety and immunogenicity of a trivalent virus-like particle vaccine against western, eastern, and Venezuelan equine encephalitis viruses: a phase 1, open-label, dose-escalation, randomised clinical trial

Author

Coates, Emily E, primary, Edupuganti, Srilatha, additional, Chen, Grace L, additional, Happe, Myra, additional, Strom, Larisa, additional, Widge, Alicia, additional, Florez, Maria Burgos, additional, Cox, Josephine H, additional, Gordon, Ingelise, additional, Plummer, Sarah, additional, Ola, Abidemi, additional, Yamshchikov, Galina, additional, Andrews, Charla, additional, Curate-Ingram, Sharon, additional, Morgan, Patricia, additional, Nagar, Shashi, additional, Collins, Matthew H, additional, Bray, Amy, additional, Nguyen, Thuy, additional, Stein, Judy, additional, Case, Christopher L, additional, Kaltovich, Florence, additional, Wycuff, Diane, additional, Liang, C Jason, additional, Carlton, Kevin, additional, Vazquez, Sandra, additional, Mascola, John R, additional, Ledgerwood, Julie E, additional, Butler, Ellie, additional, Winter, Jean, additional, Xu, Jianguo, additional, Sherman, Amy, additional, Kelley, Colleen, additional, Fredrick, Rameses, additional, Rouphael, Nadine, additional, Phadke, Varun, additional, Whitney, Cynthia, additional, Alvarez, Alicarmen, additional, Dennis, Renata, additional, Fineman, Rebecca, additional, Lankford-Turner, Pamela, additional, Yi, Sha, additional, Lai, Lilin, additional, Burch, Gena, additional, Gupta, Shanker, additional, Berkowitz, Nina, additional, Carter, Cristina, additional, Beck, Allison, additional, Larkin, Brenda, additional, Taylor, Stephanie, additional, Alger, Mandy, additional, Bahorich, Jessica, additional, Lynch Chamberlain, Amy, additional, Chang, Ya-chen, additional, Chaudhuri, Rajoshi, additional, Cooper, Jonathan, additional, Demirji, Jacob, additional, Yang, Fan, additional, Fernald, Alissa, additional, Gollapudi, Deepika, additional, Holland-Linn, Janel, additional, Kueltzo, Lisa, additional, Lee, James, additional, Liu, Jie, additional, Liu, Xun, additional, Mowery, Rachel, additional, O'Connell, Sarah, additional, Rosales-Zavala, Erwin, additional, Sands, Jason, additional, Wang, Xin, additional, Weng, Shaojie, additional, and Witter, Sara, additional

Published
2022
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25. Safety and tolerability of AAV8 delivery of a broadly neutralizing antibody in adults living with HIV: a phase 1, dose-escalation trial

Author

Casazza, Joseph P., Cale, Evan M., Narpala, Sandeep, Yamshchikov, Galina V., Coates, Emily E., Hendel, Cynthia S., Novik, Laura, Holman, LaSonji A., Widge, Alicia T., Apte, Preeti, Gordon, Ingelise, Gaudinski, Martin R., Conan-Cibotti, Michelle, Lin, Bob C., Nason, Martha C., Trofymenko, Olga, Telscher, Shinyi, Plummer, Sarah H., Wycuff, Diane, Adams, William C., Pandey, Janardan P., McDermott, Adrian, Roederer, Mario, Sukienik, Avery N., O'Dell, Sijy, Gall, Jason G., Flach, Britta, Terry, Travis L., Choe, Misook, Shi, Wei, Chen, Xuejun, Kaltovich, Florence, Saunders, Kevin O., Stein, Judy A., Doria-Rose, Nicole A., Schwartz, Richard M., Balazs, Alejandro B., Baltimore, David, Nabel, Gary J., Koup, Richard A., Graham, Barney S., Ledgerwood, Julie E., Mascola, John R., Andrews, Charla, Arthur, Anita, Awan, Seemal F., Beck, Allison, Burch, Eugeania, Burgos Florez, Maria C., Berkowitz, Nina M., Boritz, Eli A., Carlton, Kevin, Cartagena, Cora T., Carter, Christina, Chen, Grace L., Costner, Pamela, Cunningham, Jennifer, Douek, Daniel C., Eshun, Aba M., Evans, Catina, Hicks, Renunda, Houser, Katherine V., Jones, Justine, Larkin, Brenda, Le, Lam, Mendoza, Floreliz, Migueles, Stephen, Misasi, John, Nguyen, Thuy A., Ola, Abidemi, Parker, Karen, Pittman, Iris, Requilman, La’ Shawn, Rothwell, Ro Shauna, Schieber, Gretchen L., Saunders, Jamie, Sitar, Sandra, Tran, Colin, Vasilenko, Olga, Waheed, Sana, Wang, Lingshu, Wang, Xiaolin, Whalen, William, Williams, Pernell, Wu, Richard L., and Zephir, Kathy

Subjects
Adult, HIV-1, Humans, HIV Infections, General Medicine, Dependovirus, HIV Antibodies, Antibodies, Neutralizing, General Biochemistry, Genetics and Molecular Biology, Article, Broadly Neutralizing Antibodies
Abstract

Adeno-associated viral vector-mediated transfer of DNA coding for broadly neutralizing anti-HIV antibodies (bnAbs) offers an alternative to attempting to induce protection by vaccination or by repeated infusions of bnAbs. In this study, we administered a recombinant bicistronic adeno-associated virus (AAV8) vector coding for both the light and heavy chains of the potent broadly neutralizing HIV-1 antibody VRC07 (AAV8-VRC07) to eight adults living with HIV. All participants remained on effective anti-retroviral therapy (viral load (VL) 1 μg ml(−1) in three individuals. In four individuals, VRC07 serum concentrations remained stable near maximal concentration for up to 3 years of follow-up. In exploratory analyses, neutralizing activity of in vivo produced VRC07 was similar to that of in vitro produced VRC07. Three of eight participants showed a non-idiotypic anti-drug antibody (ADA) response directed against the Fab portion of VRC07. This ADA response appeared to decrease the production of serum VRC07 in two of these three participants. These data represent a proof of concept that adeno-associated viral vectors can durably produce biologically active, difficult-to-induce bnAbs in vivo, which could add valuable new tools to the fight against infectious diseases.

Published
2022

26. An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults.

Author

Widge, Alicia T., Hofstetter, Amelia R., Houser, Katherine V., Awan, Seemal F., Chen, Grace L., Burgos Florez, Maria C., Berkowitz, Nina M., Mendoza, Floreliz, Hendel, Cynthia S., Holman, LaSonji A., Gordon, Ingelise J., Apte, Preeti, Liang, C. Jason, Gaudinski, Martin R., Coates, Emily E., Strom, Larisa, Wycuff, Diane, Vazquez, Sandra, Stein, Judy A., and Gall, Jason G.

Subjects
IMMUNOGLOBULINS, NANOPARTICLES, IMMUNOLOGIC memory, HEMAGGLUTININ, VACCINE trials, SUMATRIPTAN, INFLUENZA vaccines
Abstract

Influenza vaccines could be improved by platforms inducing cross-reactive immunity. Immunodominance of the influenza hemagglutinin (HA) head in currently licensed vaccines impedes induction of cross-reactive neutralizing stem-directed antibodies. A vaccine without the variable HA head domain has the potential to focus the immune response on the conserved HA stem. This first-in-human dose-escalation open-label phase 1 clinical trial (NCT03814720) tested an HA stabilized stem ferritin nanoparticle vaccine (H1ssF) based on the H1 HA stem of A/New Caledonia/20/1999. Fifty-two healthy adults aged 18 to 70 years old enrolled to receive either 20 μg of H1ssF once (n = 5) or 60 μg of H1ssF twice (n = 47) with a prime-boost interval of 16 weeks. Thirty-five (74%) 60-μg dose participants received the boost, whereas 11 (23%) boost vaccinations were missed because of public health restrictions in the early stages of the COVID-19 pandemic. The primary objective of this trial was to evaluate the safety and tolerability of H1ssF, and the secondary objective was to evaluate antibody responses after vaccination. H1ssF was safe and well tolerated, with mild solicited local and systemic reactogenicity. The most common symptoms included pain or tenderness at the injection site (n = 10, 19%), headache (n = 10, 19%), and malaise (n = 6, 12%). We found that H1ssF elicited cross-reactive neutralizing antibodies against the conserved HA stem of group 1 influenza viruses, despite previous H1 subtype head-specific immunity. These responses were durable, with neutralizing antibodies observed more than 1 year after vaccination. Our results support this platform as a step forward in the development of a universal influenza vaccine. Fighting flu: A major goal for influenza vaccines is to elicit broadly reactive immune responses that can protect against many strains of the virus. Widge et al. and Andrews et al. report results of a phase 1 clinical trial testing a vaccine that may get closer to this goal. Widge et al. demonstrated that immunization with one or two doses of an H1 hemagglutinin stabilized stem nanoparticle (H1ssF) vaccine was safe in recipients and elicited durable neutralizing antibody responses. Andrews et al. found that memory B cell responses elicited by H1ssF vaccination were broadly cross-reactive and targeted two conserved epitopes on the H1 stem. Together, these studies highlight the potential of H1ssF and similar stem-only immunogens as influenza vaccines. —CM [ABSTRACT FROM AUTHOR]

Published
2023
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29. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults

Author

Gaudinski, Martin R., Coates, Emily E., Houser, Katherine V., Chen, Grace L., Yamshchikov, Galina, Saunders, Jamie G., Holman, LaSonji A., Gordon, Ingelise, Plummer, Sarah, Hendel, Cynthia S., Conan-Cibotti, Michelle, Lorenzo, Margarita Gomez, Sitar, Sandra, Carlton, Kevin, Laurencot, Carolyn, Bailer, Robert T., Narpala, Sandeep, McDermott, Adrian B., Namboodiri, Aryan M., Pandey, Janardan P., Schwartz, Richard M., Hu, Zonghui, Koup, Richard A., Capparelli, Edmund, Graham, Barney S., Mascola, John R., and Ledgerwood, Julie E.

Subjects
United States. National Institutes of Health, HIV (Viruses) -- Research -- Drug therapy -- Prevention, Clinical trials -- Analysis, Adults -- Health aspects, Vaccines -- Health aspects, Monoclonal antibodies -- Health aspects, HIV infection -- Health aspects -- Prevention, Biological sciences
Abstract

Background VRC01 is a human broadly neutralizing monoclonal antibody (bnMAb) against the CD4-binding site of the HIV-1 envelope glycoprotein (Env) that is currently being evaluated in a Phase IIb adult HIV-1 prevention efficacy trial. VRC01LS is a modified version of VRC01, designed for extended serum half-life by increased binding affinity to the neonatal Fc receptor. Methods and findings This Phase I dose-escalation study of VRC01LS in HIV-negative healthy adults was conducted by the Vaccine Research Center (VRC) at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD). The age range of the study volunteers was 21-50 years; 51% of study volunteers were male and 49% were female. Primary objectives were safety and tolerability of VRC01LS intravenous (IV) infusions at 5, 20, and 40 mg/kg infused once, 20 mg/kg given three times at 12-week intervals, and subcutaneous (SC) delivery at 5 mg/kg delivered once, or three times at 12-week intervals. Secondary objectives were pharmacokinetics (PK), serum neutralization activity, and development of antidrug antibodies. Enrollment began on November 16, 2015, and concluded on August 23, 2017. This report describes the safety data for the first 37 volunteers who received administrations of VRC01LS. There were no serious adverse events (SAEs) or dose-limiting toxicities. Mild malaise and myalgia were the most common adverse events (AEs). There were six AEs assessed as possibly related to VRC01LS administration, and all were mild in severity and resolved during the study. PK data were modeled based on the first dose of VRC01LS in the first 25 volunteers to complete their schedule of evaluations. The mean (±SD) serum concentration 12 weeks after one IV administration of 20 mg/kg or 40 mg/kg were 180 ± 43 [mu]g/mL (n = 7) and 326 ± 35 [mu]g/mL (n = 5), respectively. The mean (±SD) serum concentration 12 weeks after one IV and SC administration of 5 mg/kg were 40 ± 3 [mu]g/mL (n = 2) and 25 ± 5 [mu]g/mL (n = 9), respectively. Over the 5-40 mg/kg IV dose range (n = 16), the clearance was 36 ± 8 mL/d with an elimination half-life of 71 ± 18 days. VRC01LS retained its expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. Potential limitations of this study include the small sample size typical of Phase I trials and the need to further describe the PK properties of VRC01LS administered on multiple occasions. Conclusions The human bnMAb VRC01LS was safe and well tolerated when delivered intravenously or subcutaneously. The half-life was more than 4-fold greater when compared to wild-type VRC01 historical data. The reduced clearance and extended half-life may make it possible to achieve therapeutic levels with less frequent and lower-dose administrations. This would potentially lower the costs of manufacturing and improve the practicality of using passively administered monoclonal antibodies (mAbs) for the prevention of HIV-1 infection. Trial registration ClinicalTrials.gov NCT02599896, Author(s): Martin R. Gaudinski 1, Emily E. Coates 1, Katherine V. Houser 1, Grace L. Chen 1, Galina Yamshchikov 1, Jamie G. Saunders 1, LaSonji A. Holman 1, Ingelise Gordon [...]

Published
2018
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30. A Monoclonal Antibody for Malaria Prevention

Author

Gaudinski, Martin R., primary, Berkowitz, Nina M., additional, Idris, Azza H., additional, Coates, Emily E., additional, Holman, LaSonji A., additional, Mendoza, Floreliz, additional, Gordon, Ingelise J., additional, Plummer, Sarah H., additional, Trofymenko, Olga, additional, Hu, Zonghui, additional, Campos Chagas, Andrezza, additional, O’Connell, Sarah, additional, Basappa, Manjula, additional, Douek, Naomi, additional, Narpala, Sandeep R., additional, Barry, Christopher R., additional, Widge, Alicia T., additional, Hicks, Renunda, additional, Awan, Seemal F., additional, Wu, Richard L., additional, Hickman, Somia, additional, Wycuff, Diane, additional, Stein, Judy A., additional, Case, Christopher, additional, Evans, Brian P., additional, Carlton, Kevin, additional, Gall, Jason G., additional, Vazquez, Sandra, additional, Flach, Britta, additional, Chen, Grace L., additional, Francica, Joseph R., additional, Flynn, Barbara J., additional, Kisalu, Neville K., additional, Capparelli, Edmund V., additional, McDermott, Adrian, additional, Mascola, John R., additional, Ledgerwood, Julie E., additional, and Seder, Robert A., additional

Published
2021
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31. Limited Flavivirus Cross-Reactive Antibody Responses Elicited by a Zika Virus Deoxyribonucleic Acid Vaccine Candidate in Humans

Author

Burgomaster, Katherine E, primary, Foreman, Bryant M, additional, Aleshnick, Maya A, additional, Larman, Bridget C, additional, Gordon, David N, additional, Maciejewski, Sonia, additional, Morabito, Kaitlyn M, additional, Ledgerwood, Julie E, additional, Gaudinski, Martin R, additional, Chen, Grace L, additional, Mascola, John R, additional, Debbink, Kari, additional, Dowd, Kimberly A, additional, Graham, Barney S, additional, and Pierson, Theodore C, additional

Published
2021
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32. Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses

Author

Mukhamedova, Maryam, primary, Wrapp, Daniel, additional, Shen, Chen-Hsiang, additional, Gilman, Morgan S.A., additional, Ruckwardt, Tracy J., additional, Schramm, Chaim A., additional, Ault, Larissa, additional, Chang, Lauren, additional, Derrien-Colemyn, Alexandrine, additional, Lucas, Sarah A.M., additional, Ransier, Amy, additional, Darko, Samuel, additional, Phung, Emily, additional, Wang, Lingshu, additional, Zhang, Yi, additional, Rush, Scott A., additional, Madan, Bharat, additional, Stewart-Jones, Guillaume B.E., additional, Costner, Pamela J., additional, Holman, LaSonji A., additional, Hickman, Somia P., additional, Berkowitz, Nina M., additional, Doria-Rose, Nicole A., additional, Morabito, Kaitlyn M., additional, DeKosky, Brandon J., additional, Gaudinski, Martin R., additional, Chen, Grace L., additional, Crank, Michelle C., additional, Misasi, John, additional, Sullivan, Nancy J., additional, Douek, Daniel C., additional, Kwong, Peter D., additional, Graham, Barney S., additional, McLellan, Jason S., additional, and Mascola, John R., additional

Published
2021
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35. Distinct neutralizing antibody correlates of protection among related Zika virus vaccines identify a role for antibody quality

Author

Maciejewski, Sonia, primary, Ruckwardt, Tracy J., additional, Morabito, Kaitlyn M., additional, Foreman, Bryant M., additional, Burgomaster, Katherine E., additional, Gordon, David N., additional, Pelc, Rebecca S., additional, DeMaso, Christina R., additional, Ko, Sung-Youl, additional, Fisher, Brian E., additional, Yang, Eun Sung, additional, Nair, Deepika, additional, Foulds, Kathryn E., additional, Todd, John Paul, additional, Kong, Wing-Pui, additional, Roy, Vicky, additional, Aleshnick, Maya, additional, Speer, Scott D., additional, Bourne, Nigel, additional, Barrett, Alan D., additional, Nason, Martha C., additional, Roederer, Mario, additional, Gaudinski, Martin R., additional, Chen, Grace L., additional, Dowd, Kimberly A., additional, Ledgerwood, Julie E., additional, Alter, Galit, additional, Mascola, John R., additional, Graham, Barney S., additional, and Pierson, Theodore C., additional

Published
2020
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36. Molecular Dissection Of Human Antibody Responses Following Prefusion-Stabilized RSV F Vaccination

Author

Mukhamedova, Maryam, primary, Wrapp, Daniel, additional, Shen, Chen-Hsiang, additional, Gilman, Morgan S.A., additional, Ruckwardt, Tracy, additional, Schramm, Chaim A., additional, Ault, Larissa, additional, Chang, Lauren, additional, Derrien-Colemyn, Alexandrine, additional, Lucas, Sarah A.M., additional, Ransier, Amy, additional, Darko, Samuel, additional, Phung, Emily, additional, Wang, Lingshu, additional, Zhang, Yi, additional, Rush, Scott A., additional, Madan, Bharat, additional, Stewart-Jones, Guillaume B. E., additional, Costner, Pamela J., additional, Holman, LaSonji A., additional, Hickman, Somia P., additional, Berkowitz, Nina M., additional, Doria-Rose, Nicole, additional, Morabito, Kaitlyn M., additional, DeKosky, Brandon J., additional, Gaudinski, Martin R., additional, Chen, Grace L., additional, Crank, Michelle C., additional, Misasi, John, additional, Sullivan, Nancy J., additional, Douek, Daniel C., additional, Kwong, Peter D., additional, Graham, Barney S., additional, McLellan, Jason S., additional, and Mascola, John, additional

Published
2020
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38. Case-Based Curriculum With Integrated Smartphone Applications Improves Internal Medicine Resident Knowledge Of Contraceptive Care

Author

Bachorik, Alexandra, Nemer, Michelle K, Chen, Grace L, Alexander, Cristina Baseggio, Pelletier, Stephen R, Pace, Lydia E, and Shields, Helen M

Subjects
medical education-graduate, medical education-curriculum development/evaluation, contraception, active learning, education, ComputingMilieux_COMPUTERSANDEDUCATION, Advances in Medical Education and Practice, reproductive health, Original Research
Abstract

Alexandra Bachorik,1,2 Michelle K Nemer,3 Grace L Chen,4 Cristina Baseggio Alexander,1,2 Stephen R Pelletier,2 Lydia E Pace,2,4 Helen M Shields2,5 1Division of General Internal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USA; 3Department of Medicine, Metro Health Medical Center, Case Western Reserve School of Medicine, Cleveland, OH, USA; 4Division of Women’s Health, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 5Division of Medical Communications, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USACorrespondence: Alexandra BachorikSection of General Internal Medicine, Boston University School of Medicine, 801 Massachusetts Ave, 1st Fl, Boston, MA 02118, USATel +12408999052Fax +16176388096Email alexandra.elise.bachorik@gmail.comBackground: Contraception is an essential preventive service for all women. However, the literature suggests that internal medicine residents have low levels of confidence and knowledge of contraceptive care.Objective: We designed and implemented a novel contraception curriculum promoting active, collaborative learning. We sought to evaluate whether this curriculum improved internal medicine resident knowledge of and comfort with contraceptive care through the administration of pre-/post-surveys.Methods: Our curriculum was delivered in a two-hour session as part of the mandatory ambulatory curriculum for internal medicine interns at our institution in the academic year 2017–2018. Interns were provided with select online resources and two smartphone applications at the beginning of the session, which they then used in case-based small group work. Small group work was followed by a large group case review, co-facilitated by OB/GYN and internal medicine faculty.Results: Thirty-eight participants completed surveys assessing knowledge of and comfort with contraceptive care immediately before and after the curriculum; 20 participants completed surveys assessing the same domains 4–6 months after the curriculum. Data from surveys administered immediately post-curriculum demonstrated significant improvements in knowledge about and comfort with counseling about, assessing medical eligibility for, and initiating multiple forms of contraception. Many of these improvements in knowledge and comfort were maintained on follow-up surveys 4–6 months following the curriculum.Conclusion: Our case-based curriculum with integrated smartphone applications resulted in significant improvements in internal medicine resident knowledge of and comfort with the key skills of contraceptive care. In contrast to active, collaborative learning methodologies such as the flipped classroom, our methodology supports active, collaborative learning without requiring advance learner preparation, and is thus well suited to the time constraints of the graduate medical education setting. Our methodology is readily translatable to other clinical topics and residency curricula.Keywords: reproductive health, medical education-graduate, medical education-curriculum development/evaluation, active learning, contraception

Published
2019

39. Cloning and expression of a gene encoding a bacterial enzyme for decontamination of organophosphorus nerve agents and nucleotide sequence of the enzyme

Author

Cheng, Tu-Chen, Harvey, Steven P., and Chen, Grace L.

Subjects
Enzyme kinetics -- Research, Genetic code -- Identification and classification, Gene expression -- Analysis, Cloning -- Research, Organophosphorus compounds -- Analysis, Biological sciences
Abstract

The gene for organophosphorus anhydrolase (OPAA-2) is cloned into Escherichia coli and sequenced to investigate the natural function of OPA anhydrolase enzymes. Results show that OPAA-2 is similar to a 647-amino-acid sequence produced by an open reading frame known as the E. coli pepQ gene. This finding indicates that the OPAA-2 enzyme may play an essential role in the mechanism of hydrolysis.

Published
1996

40. Case-Based Curriculum With Integrated Smartphone Applications Improves Internal Medicine Resident Knowledge Of Contraceptive Care

Author

Bachorik,Alexandra, Nemer,Michelle K, Chen,Grace L, Alexander,Cristina Baseggio, Pelletier,Stephen R, Pace,Lydia E, Shields,Helen M, Bachorik,Alexandra, Nemer,Michelle K, Chen,Grace L, Alexander,Cristina Baseggio, Pelletier,Stephen R, Pace,Lydia E, and Shields,Helen M

Abstract

Alexandra Bachorik,1,2 Michelle K Nemer,3 Grace L Chen,4 Cristina Baseggio Alexander,1,2 Stephen R Pelletier,2 Lydia E Pace,2,4 Helen M Shields2,5 1Division of General Internal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USA; 3Department of Medicine, Metro Health Medical Center, Case Western Reserve School of Medicine, Cleveland, OH, USA; 4Division of Women’s Health, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 5Division of Medical Communications, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USACorrespondence: Alexandra BachorikSection of General Internal Medicine, Boston University School of Medicine, 801 Massachusetts Ave, 1st Fl, Boston, MA 02118, USATel +12408999052Fax +16176388096Email alexandra.elise.bachorik@gmail.comBackground: Contraception is an essential preventive service for all women. However, the literature suggests that internal medicine residents have low levels of confidence and knowledge of contraceptive care.Objective: We designed and implemented a novel contraception curriculum promoting active, collaborative learning. We sought to evaluate whether this curriculum improved internal medicine resident knowledge of and comfort with contraceptive care through the administration of pre-/post-surveys.Methods: Our curriculum was delivered in a two-hour session as part of the mandatory ambulatory curriculum for internal medicine interns at our institution in the academic year 2017–2018. Interns were provided with select online resources and two smartphone applications at the beginning of the session, which they then used in case-based small group work. Small group work was followed by a large group case review, co-facilitated by OB/GYN and internal medicine faculty.Results: Thirty-eight participants completed surveys assessing knowledge of and comfort with contraceptive care immediatel

Published
2019

42. Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial

Author

Gaudinski, Martin R, primary, Houser, Katherine V, additional, Doria-Rose, Nicole A, additional, Chen, Grace L, additional, Rothwell, Ro Shauna S, additional, Berkowitz, Nina, additional, Costner, Pamela, additional, Holman, LaSonji A, additional, Gordon, Ingelise J, additional, Hendel, Cynthia S, additional, Kaltovich, Florence, additional, Conan-Cibotti, Michelle, additional, Gomez Lorenzo, Margarita, additional, Carter, Cristina, additional, Sitar, Sandra, additional, Carlton, Kevin, additional, Gall, Jason, additional, Laurencot, Carolyn, additional, Lin, Bob C, additional, Bailer, Robert T, additional, McDermott, Adrian B, additional, Ko, Sung-Youl, additional, Pegu, Amarendra, additional, Kwon, Young D, additional, Kwong, Peter D, additional, Namboodiri, Aryan M, additional, Pandey, Janardan P, additional, Schwartz, Richard, additional, Arnold, Frank, additional, Hu, Zonghui, additional, Zhang, Lily, additional, Huang, Yunda, additional, Koup, Richard A, additional, Capparelli, Edmund V, additional, Graham, Barney S, additional, Mascola, John R, additional, Ledgerwood, Julie E, additional, Mendoza, Floreliz, additional, Novik, Laura, additional, Zephir, Kathy, additional, Whalen, William, additional, Larkin, Brenda, additional, Saunders, Jamie, additional, Cunningham, Jennifer, additional, Levinson, Carol, additional, Wang, Xiaolin, additional, Plummer, Sarah, additional, Victorino, Milalynn, additional, Ola, Abidemi, additional, Boyd, Catina, additional, Jayasinghe, Nilusha, additional, Apte, Preeti, additional, Cartagena, Cora Trelles, additional, Hicks, Renunda, additional, Williams, Pernell, additional, Vasilenko, Olga, additional, Yamshchikov, Galina, additional, Florez, Maria Burgos, additional, Pittman, Iris, additional, Gama, Lucio, additional, Casazza, Joseph, additional, DeCederfelt, Hope, additional, Cheng, KC, additional, and Stein, Judy, additional

Published
2019
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43. Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin

Author

Andrews, Sarah F., primary, Chambers, Michael J., additional, Schramm, Chaim A., additional, Plyler, Jason, additional, Raab, Julie E., additional, Kanekiyo, Masaru, additional, Gillespie, Rebecca A., additional, Ransier, Amy, additional, Darko, Sam, additional, Hu, Jianfei, additional, Chen, Xuejun, additional, Yassine, Hadi M., additional, Boyington, Jeffrey C., additional, Crank, Michelle C., additional, Chen, Grace L., additional, Coates, Emily, additional, Mascola, John R., additional, Douek, Daniel C., additional, Graham, Barney S., additional, Ledgerwood, Julie E., additional, and McDermott, Adrian B., additional

Published
2019
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44. Safety, tolerability, pharmacokinetics, and immunogenicity of the therapeutic monoclonal antibody mAb114 targeting Ebola virus glycoprotein (VRC 608): an open-label phase 1 study

Author

Gaudinski, Martin R, primary, Coates, Emily E, additional, Novik, Laura, additional, Widge, Alicia, additional, Houser, Katherine V, additional, Burch, Eugeania, additional, Holman, LaSonji A, additional, Gordon, Ingelise J, additional, Chen, Grace L, additional, Carter, Cristina, additional, Nason, Martha, additional, Sitar, Sandra, additional, Yamshchikov, Galina, additional, Berkowitz, Nina, additional, Andrews, Charla, additional, Vazquez, Sandra, additional, Laurencot, Carolyn, additional, Misasi, John, additional, Arnold, Frank, additional, Carlton, Kevin, additional, Lawlor, Heather, additional, Gall, Jason, additional, Bailer, Robert T, additional, McDermott, Adrian, additional, Capparelli, Edmund, additional, Koup, Richard A, additional, Mascola, John R, additional, Graham, Barney S, additional, Sullivan, Nancy J, additional, Ledgerwood, Julie E, additional, Hendel, Cynthia Starr, additional, Plummer, Sarah H., additional, Costner, Pamela, additional, Saunders, Jamie, additional, Mendoza, Floreliz, additional, Eshun, Aba Mensima, additional, Casazza, Joseph, additional, Ola, Abidemi, additional, Whalen, William, additional, Wang, Xiaolin, additional, Cunningham, Jennifer, additional, Vasilenko, Olga, additional, Boyd, Catina R., additional, Trofymenko, Olga, additional, Burgos Florez, Maria Claudia, additional, Hickman, Somia, additional, Rothwell, Ro Shauna, additional, Pittman, Iris R, additional, Le, Lam Ngan, additional, Larkin, Brenda D, additional, Cox, Josephine H, additional, Apte, Preeti J, additional, Hicks, Renunda T, additional, Trelles Cartagena, Cora, additional, Williams, Pernell V, additional, Requilman, LaShawn, additional, Nguyen, Thuy, additional, Tran, Colin, additional, Conan-Cibotti, Michelle, additional, Stein, Judy, additional, and Beresnev, Tatiana, additional

Published
2019
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45. Effect of a Chikungunya Virus-Like Particle Vaccine on Safety and Tolerability Outcomes: A Randomized Clinical Trial.

Author

Chen, Grace L., Coates, Emily E., Plummer, Sarah H., Carter, Cristina A., Berkowitz, Nina, Conan-Cibotti, Michelle, Cox, Josephine H., Beck, Allison, O'Callahan, Mark, Andrews, Charla, Gordon, Ingelise J., Larkin, Brenda, Lampley, Rebecca, Kaltovich, Florence, Gall, Jason, Carlton, Kevin, Mendy, Jason, Haney, Doug, May, Jeanine, and Bray, Amy

Subjects
*VIRAL vaccines, *CHIKUNGUNYA, *IMMUNOGLOBULINS, *INTRAMUSCULAR injections, *RANDOMIZED controlled trials, *BLIND experiment, *NEUTRALIZATION tests, *STATISTICAL sampling, *CHIKUNGUNYA virus
Abstract

Importance: Chikungunya virus (CHIKV) is a mosquito-borne Alphavirus prevalent worldwide. There are currently no licensed vaccines or therapies.Objective: To evaluate the safety and tolerability of an investigational CHIKV virus-like particle (VLP) vaccine in endemic regions.Design, Setting, and Participants: This was a randomized, placebo-controlled, double-blind, phase 2 clinical trial to assess the vaccine VRC-CHKVLP059-00-VP (CHIKV VLP). The trial was conducted at 6 outpatient clinical research sites located in Haiti, Dominican Republic, Martinique, Guadeloupe, and Puerto Rico. A total of 400 healthy adults aged 18 through 60 years were enrolled after meeting eligibility criteria. The first study enrollment occurred on November 18, 2015; the final study visit, March 6, 2018.Interventions: Participants were randomized 1:1 to receive 2 intramuscular injections 28 days apart (20 µg, n = 201) or placebo (n = 199) and were followed up for 72 weeks.Main Outcomes and Measures: The primary outcome was the safety (laboratory parameters, adverse events, and CHIKV infection) and tolerability (local and systemic reactogenicity) of the vaccine, and the secondary outcome was immune response by neutralization assay 4 weeks after second vaccination.Results: Of the 400 randomized participants (mean age, 35 years; 199 [50%] women), 393 (98%) completed the primary safety analysis. All injections were well tolerated. Of the 16 serious adverse events unrelated to the study drugs, 4 (25%) occurred among 4 patients in the vaccine group and 12 (75%) occurred among 11 patients in the placebo group. Of the 16 mild to moderate unsolicited adverse events that were potentially related to the drug, 12 (75%) occurred among 8 patients in the vaccine group and 4 (25%) occurred among 3 patients in the placebo group. All potentially related adverse events resolved without clinical sequelae. At baseline, there was no significant difference between the effective concentration (EC50)-which is the dilution of sera that inhibits 50% infection in viral neutralization assay-geometric mean titers (GMTs) of neutralizing antibodies of the vaccine group (46; 95% CI, 34-63) and the placebo group (43; 95% CI, 32-57). Eight weeks following the first administration, the EC50 GMT in the vaccine group was 2005 (95% CI, 1680-2392) vs 43 (95% CI, 32-58; P < .001) in the placebo group. Durability of the immune response was demonstrated through 72 weeks after vaccination.Conclusions and Relevance: Among healthy adults in a chikungunya endemic population, a virus-like particle vaccine compared with placebo demonstrated safety and tolerability. Phase 3 trials are needed to assess clinical efficacy.Trial Registration: ClinicalTrials.gov Identifier: NCT02562482. [ABSTRACT FROM AUTHOR]

Published
2020
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47. Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials

Author

Gaudinski, Martin R, primary, Houser, Katherine V, additional, Morabito, Kaitlyn M, additional, Hu, Zonghui, additional, Yamshchikov, Galina, additional, Rothwell, Ro Shauna, additional, Berkowitz, Nina, additional, Mendoza, Floreliz, additional, Saunders, Jamie G, additional, Novik, Laura, additional, Hendel, Cynthia S, additional, Holman, LaSonji A, additional, Gordon, Ingelise J, additional, Cox, Josephine H, additional, Edupuganti, Srilatha, additional, McArthur, Monica A, additional, Rouphael, Nadine G, additional, Lyke, Kirsten E, additional, Cummings, Ginny E, additional, Sitar, Sandra, additional, Bailer, Robert T, additional, Foreman, Bryant M, additional, Burgomaster, Katherine, additional, Pelc, Rebecca S, additional, Gordon, David N, additional, DeMaso, Christina R, additional, Dowd, Kimberly A, additional, Laurencot, Carolyn, additional, Schwartz, Richard M, additional, Mascola, John R, additional, Graham, Barney S, additional, Pierson, Theodore C, additional, Ledgerwood, Julie E, additional, Chen, Grace L, additional, Plummer, Sarah, additional, Costner, Pamela, additional, Zephir, Kathryn, additional, Casazza, Joseph, additional, Ola, Abidemi, additional, Victorino, Milalynn, additional, Levinson, Carol, additional, Whalen, William, additional, Wang, Xiaolin, additional, Cunningham, Jennifer, additional, Vasilenko, Olga, additional, Burgos Florez, Maria, additional, Hickman, Somia, additional, Pittman, Iris, additional, Le, Lam, additional, Larkin, Brenda, additional, Andrews, Charla, additional, Apte, Preeti, additional, Hicks, Renunda, additional, Trelles Cartagena, Cora, additional, Williams, Pernell, additional, Boyd, Catina R, additional, Conan-Cibotti, Michelle, additional, Stein, Judy, additional, Kaltovich, Florence, additional, DeCederfelt, Hope, additional, McAdams, Stacey, additional, Renehan, Phyllis, additional, Chen, Wilbur, additional, Greenberg, Nancy, additional, Wymer, Nancy, additional, Wadsworth, Linda, additional, Billington, Melissa, additional, Robinson, Toni, additional, Boyce, Colleen, additional, Pa'ahana Brown, Faith, additional, Chrisley, Lisa, additional, Kwon, Alyson, additional, Patel, Prashant, additional, Kominou, Panagoita, additional, Dorsey, Brenda, additional, Eddington, Staci, additional, Telscher, Shinyi, additional, Lee, Myoughee, additional, Mosely, Regina, additional, Ross, April, additional, Ford, Geoffrey, additional, Domjahn, Briyana, additional, Xu, Jianguo, additional, Beck, Allison, additional, Fineman, Rebecca, additional, Heeke, Shiela, additional, Winter, Jean, additional, Nagar, Shashi, additional, Kelley, Colleen, additional, and Mulligan, Mark, additional

Published
2018
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50. An open‐label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults

Author

Talaat, Kawsar R., Karron, Ruth A., Liang, Philana H., McMahon, Bridget A., Luke, Catherine J., Thumar, Bhagvanji, Chen, Grace L., Min, Ji‐Young, Lamirande, Elaine W., Jin, Hong, Coelingh, Kathy L., Kemble, George W., and Subbarao, Kanta

Subjects
Adult, Male, H2N2, neuraminidase inhibition, Vaccination, Original Articles, Antibodies, Viral, Vaccines, Attenuated, Virus Replication, Influenza A Virus, H2N2 Subtype, Virus Shedding, Young Adult, Treatment Outcome, live attenuated influenza vaccines, Influenza Vaccines, Influenza, Human, Humans, Original Article, Female, human, influenza vaccine, influenza
Abstract

Please cite this paper as: Talaat et al. (2012) An open‐label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00350.x. Background Live attenuated influenza vaccines (LAIV) against a variety of strains of pandemic potential are being developed and tested. We describe the results of an open‐label phase I trial of a live attenuated H2N2 virus vaccine. Objectives To evaluate the safety, infectivity, and immunogenicity of a live attenuated H2N2 influenza virus vaccine. Participants/methods The A/Ann Arbor/6/60 (H2N2) virus used in this study is the attenuated, cold‐adapted, temperature‐sensitive strain that provides the genetic backbone of seasonal LAIV (MedImmune). We evaluated the safety, infectivity, and immunogenicity of two doses of 107 TCID50 of this vaccine administered by nasal spray 4 weeks apart to normal healthy seronegative adults. Results Twenty‐one participants received a first dose of the vaccine; 18 participants received a second dose. No serious adverse events occurred during the trial. The most common adverse events after vaccination were headache and musculoskeletal pain. The vaccine was restricted in replication: 24% and 17% had virus detectable by culture or rRT‐PCR after the first and second dose, respectively. Antibody responses to the vaccine were also restricted: 24% of participants developed an antibody response as measured by either hemagglutination‐inhibition assay (10%), or ELISA for H2 HA‐specific serum IgG (24%) or IgA (16%) after either one or two doses. None of the participants had a neutralizing antibody response. Vaccine‐specific IgG‐secreting cells as measured by enzyme‐linked immunospot increased from a mean of 0·5 to 2·0/106 peripheral blood mononuclear cells (PBMCs); vaccine‐specific IgA‐secreting cells increased from 0·1 to 0·5/106 PBMCs. Conclusions The live attenuated H2N2 1960 AA ca vaccine demonstrated a safety profile consistent with seasonal trivalent LAIV but was restricted in replication and minimally immunogenic in healthy seronegative adults.

Published
2012

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