Neutralizing and binding antibodies are a correlate of risk of COVID-19 in the CoVPN 3008 study in people with HIV
Abstract
Abstract People with HIV (PWH) are understudied in COVID-19 vaccine trials, leaving knowledge gaps on whether the identified immune correlates of protection also hold in PWH. CoVPN 3008 (NCT05168813) enrolled predominantly PWH and reported lower COVID-19 incidence for a Hybrid vs. Vaccine Group (baseline SARS-CoV-2-positive and one mRNA-1273 dose vs. negative and two doses). Using case-cohort sampling, antibody markers at enrolment (M0) and four weeks post-final vaccination (Peak) are assessed as immune correlates of COVID-19. For the Hybrid Group [n = 287 (195 PWH)], all M0 markers inversely correlate with COVID-19 through 230 days post-Peak, with 50% inhibitory dilution BA.4/5 neutralizing antibody titer (nAb-ID50 BA.4/5) the strongest and only independent correlate (HR per 10-fold increase=0.46, 95% CI 0.28, 0.75; P = 0.002). For the Vaccine Group [n = 115 (86 PWH)], Peak nAb-ID50 BA.4/5 correlates with reduced COVID-19 risk (1.9%, 1.1%, and 0.3% at titers 10, 100, and 1000 AU/ml) through 92, but not 165, days post-Peak. Using multivariable Cox analysis of binding and nAb, nAb titers predict COVID-19 in PWH. Two doses of a 100-µg Ancestral strain mRNA vaccine in baseline-SARS-CoV-2-negative individuals elicit sufficient cross-reacting Omicron antibodies to reduce COVID-19 incidence for 90 days post-Peak, but viral evolution and waning antibodies abrogate this protection thereafter.
Article Details
Authors (108)
Nonhlanhla N. Mkhize
Bo Zhang
Caroline Brackett
Peter James Elyanu
Asa Tapley
Sufia Dadabhai
Jiani Hu
Bich T. N. Do
Daniel J. Schuster
Jack Heptinstall
Sheetal Sawant
Kelly Seaton
Marcella Sarzotti-Kelsoe
Aaron Hudson
Yutong Jin
Sinethemba Bhebhe
Haajira Kaldine
Prudence Kgagudi
Tandile Modise
Nyaradzo M. Mgodi
University of Zimbabwe Clinical Trials Research Centre, Harare
Jessica Andriesen
April K. Randhawa
Leigh H. Fisher
Jia Jin Kee
Craig A. Magaret
James Peng
Avi Kenny
Lindsay N. Carpp
Zhe Chen
Gladstone Institutes, San Francisco, CA, USA.
Siyu Heng
Manuel Villaran
Azwidihwi Takalani
Bert Le Roux
Eduan Wilkinson
Jackline Odhiambo
Parth Shah
Laura Polakowski
Margaret Yacovone
Taraz Samandari
Zvavahera Chirenje
Joseph Makhema
Ethel Kamuti
Katanekwa Njekwa
Harriet Nuwagaba-Biribonwoha
Allan Baguma
Sharlaa Badal-Faesen
William Brumskine
Soritha Coetzer
Rodney Dawson
Sinéad Delany-Moretlwe
Andreas Henri Diacon
Samantha Fry
Katherine Gill
Anda Madikida
Zaheer Ahmed Ebrahim Hoosain
Mina C. Hosseinipour
Mubiana Inambao
Craig Innes
Steve Innes
Dishiki Kalonji
Humphrey Mwape
Priya Kassim
Melvin C. Kamanga
William Kilembe
Fatima Laher
Mookho Malahleha
Vongane Louisa Maluleke
Grace Mboya
Philister Adhiambo Madiega
Kirsten McHarry
Essack Mitha
Yajna Duki
Pamela Mda
Moroesi Moerane
Tumelo Moloantoa
Simpson Nuwamanya
Sharana Mahomed
Vimla Naicker
Anusha Nana
Annet Nanvubya
Barbarah Kawoozo
Maphoshane Nchabeleng
Walter Otieno
Elsje Louise Potgieter
Disebo Potloane
Zelda Punt
Jamil Said
Yashna Singh
Sheetal Kassim
Dorothie van der Vendt
Mohammed Siddique Tayob
Yacoob Vahed
Deo Ogema Wabwire
James G. Kublin
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle
Linda-Gail Bekker
Lawrence Corey
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Glenda E. Gray
Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg
Yunda Huang
Philip Kotze
Nigel Garrett
John Hural
Guido Ferrari
Erica Andersen-Nissen
David Montefiori
Penny L. Moore
M. Juliana McElrath
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Georgia D. Tomaras
Peter B. Gilbert