Phase I/II, open-label trial of safety and immunogenicity of meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine in human immunodeficiency virus-infected adolescents
George K Siberry, Paige L Williams, Jorge Lujan-Zilbermann, Meredith G Warshaw, Stephen A Spector, Michael D Decker, Barbara E Heckman, Emily F Demske, Jennifer S Read, Patrick Jean-Philippe, William Kabat, Sharon Nachman, IMPAACT P1065 Protocol Team, Kenneth D Braun Jr, Greg Gilmet, Adam Manzella, Donna Picard, Paul Tran, Scott Watson, James Oleske, Arlene Bardeguez, Arry Dieudonne, Linda Bettica, Nicole Falgout, Joseph Geffen, Karin Nielsen, Jaime Deville, Chivon Jackson, Shelley Buscher, Faith Mingala, Mary E Paul, Alice Higgins, Andrea Jurgrau, Marc Foca, Seydi Vasquez, Gwendolyn B Scott, Charles D Mitchell, Patricia Bryan, Claudia Florez, Rolando M Viani, Jeanne Manning, Kim Norris, Margaret Donnelly, Joan Wilson, Mary Jo Hassett, Kathleen McGann, Aditya Kaul, Sulachni Chandwani, William Borkowsky, Nagamah Deygoo, Andrew Wiznia, Marlene Burey, Jorge Sansary, Francisco Reinoso, Ann J Melvin, Lisa M Frenkel, Joycelyn Thomas, Denise Casey, Carolyn Graisbery, Gail Lewis, Carina Rodriguez, Midnela Acevedo-Flores, Milagros González-Díaz, Lizbeth Fábregas, Orlando Alonso, Denise Ferraro, Erin Infanzon, Michele Kelly, Ellen C Moore, Chokechai Rongkavilit, Elizabeth Secord, Ulyssa Hancock, Sohail Rana, Helga Finke-Castro, Meseret Deressa, Connie Nguyen, James Homans, Andrea Kovacs, LaShonda Spencer, Michael Neely, Mobeen H Rathore, Nizar M Araqa, Kathy Thoma, Chas Griggs, Myron J Levin, Emily Barr, Megan Canon, Jason Child, Ana M Puga, Kathleen Graham, Kevin Brown, Carol Owens, Geoffrey A Weinberg, Barbra Murante, Susan Laverty, Francis Gigliotti, Marvin Belzer, Johanna Olson, Diane Tucker, Nancy Flores, Jill Utech, Nehali Patel, Lennie Lott, Aditya H Gaur, Irma Febo, Licette Lugo, Ruth Santos, Maritza Cruz, Steven D Douglas, Richard M Rutstein, Carol A Vincent, Patricia C Coburn, Aida Matias, Mavis Dummitt, Stefan Hagmann, Murli Purswani, Richard Moriarty, Katherine Luzuriaga, Jesica Pagano-Therrien, Ram Yogev, George K Siberry, Paige L Williams, Jorge Lujan-Zilbermann, Meredith G Warshaw, Stephen A Spector, Michael D Decker, Barbara E Heckman, Emily F Demske, Jennifer S Read, Patrick Jean-Philippe, William Kabat, Sharon Nachman, IMPAACT P1065 Protocol Team, Kenneth D Braun Jr, Greg Gilmet, Adam Manzella, Donna Picard, Paul Tran, Scott Watson, James Oleske, Arlene Bardeguez, Arry Dieudonne, Linda Bettica, Nicole Falgout, Joseph Geffen, Karin Nielsen, Jaime Deville, Chivon Jackson, Shelley Buscher, Faith Mingala, Mary E Paul, Alice Higgins, Andrea Jurgrau, Marc Foca, Seydi Vasquez, Gwendolyn B Scott, Charles D Mitchell, Patricia Bryan, Claudia Florez, Rolando M Viani, Jeanne Manning, Kim Norris, Margaret Donnelly, Joan Wilson, Mary Jo Hassett, Kathleen McGann, Aditya Kaul, Sulachni Chandwani, William Borkowsky, Nagamah Deygoo, Andrew Wiznia, Marlene Burey, Jorge Sansary, Francisco Reinoso, Ann J Melvin, Lisa M Frenkel, Joycelyn Thomas, Denise Casey, Carolyn Graisbery, Gail Lewis, Carina Rodriguez, Midnela Acevedo-Flores, Milagros González-Díaz, Lizbeth Fábregas, Orlando Alonso, Denise Ferraro, Erin Infanzon, Michele Kelly, Ellen C Moore, Chokechai Rongkavilit, Elizabeth Secord, Ulyssa Hancock, Sohail Rana, Helga Finke-Castro, Meseret Deressa, Connie Nguyen, James Homans, Andrea Kovacs, LaShonda Spencer, Michael Neely, Mobeen H Rathore, Nizar M Araqa, Kathy Thoma, Chas Griggs, Myron J Levin, Emily Barr, Megan Canon, Jason Child, Ana M Puga, Kathleen Graham, Kevin Brown, Carol Owens, Geoffrey A Weinberg, Barbra Murante, Susan Laverty, Francis Gigliotti, Marvin Belzer, Johanna Olson, Diane Tucker, Nancy Flores, Jill Utech, Nehali Patel, Lennie Lott, Aditya H Gaur, Irma Febo, Licette Lugo, Ruth Santos, Maritza Cruz, Steven D Douglas, Richard M Rutstein, Carol A Vincent, Patricia C Coburn, Aida Matias, Mavis Dummitt, Stefan Hagmann, Murli Purswani, Richard Moriarty, Katherine Luzuriaga, Jesica Pagano-Therrien, Ram Yogev
Abstract
Background: Quadrivalent meningococcal polysaccharide conjugate vaccine (MCV4) is routinely recommended for healthy youth in the United States, but there are no data about its use in HIV-infected people.
Methods: P1065 is a Phase I/II trial of MCV4 safety and immunogenicity in HIV-infected children and youth performed at 27 US sites of the IMPAACT network. All youth (11-24 years old) received 1 dose of open-label MCV4 at entry. Standardized questionnaires were used to evaluate safety. Baseline protective immunity was defined as rabbit serum bactericidal antibody (rSBA) titer > or = 1:128. Immunogenic response was defined as a > or = 4-fold rise in rSBA against each meningococcal serogroup. Multivariable logistic regression analysis was used to evaluate the association of demographic and clinical characteristics on immunogenic response to serogroup C.
Results: Among 319 subjects who received MCV4, 10 (3.1%) reported immediate adverse events which were local and mild, and 7 (2.2%) experienced Grade > or = 3 adverse events, unrelated to vaccine. The 305 subjects with serologic data had a median age of 17 years and were 59% male, 50% Black, and 38% Latino. Subjects were stratified by entry CD4%: 12%, CD4 <15%; 40%, 15% to 24%; and 48%, > or = 25%. Baseline protective immunity varied by serogroup: A, 41%; C, 11%; W-135, 15%; Y, 35% The immunogenic response rates to serogroups A, C, W-135, and Y were 68%, 52%, 73%, and 63%, respectively. In multivariable logistic regression models, lower entry CD4%, higher entry viral load, and CDC Class B/C diagnosis were associated with significantly lower odds of response to serogroup C.
Conclusion: Many HIV-infected youth naturally acquire meningococcal immunity. MCV4 is safe and immunogenic in HIV-infected youth, but response rates are lower than in healthy youth, particularly for those with more advanced HIV clinical, immunologic, and virologic status.
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Source: PubMed