Neutralizing and binding antibodies are a correlate of risk of COVID-19 in the CoVPN 3008 study in people with HIV
- 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
- Jessica Andriesen
- April K. Randhawa
- Leigh H. Fisher
- Jia Jin Kee
- Craig A. Magaret
- James Peng
- Avi Kenny
- Lindsay N. Carpp
- Zhe Chen
- 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
- Sinead Delany-Moretlwe
2025-10-06
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.