Browsing by Author "Polakowski, Laura"

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Hybrid versus vaccine immunity of mRNA-1273 among people living with HIV in East and Southern Africa: a prospective cohort analysis from the multicentre CoVPN 3008 (Ubuntu) study.
(2025-Feb) Garrett, Nigel; Tapley, Asa; Hudson, Aaron; Dadabhai, Sufia; Zhang, Bo; Mgodi, Nyaradzo M.; Andriesen, Jessica; Takalani, Azwidihwi; Fisher, Leigh H.; Kee, Jia J.; Magaret, Craig A.; Villaran, Manuel; Hural, John; Andersen-Nissen, Erica; Ferarri, Guido; Miner, Maurine D.; Le Roux, Bert; Wilkinson, Eduan; Lessells, Richard; de Oliveira, Tulio; Odhiambo, Jackline; Shah, Parth; Polakowski, Laura; Yacovone, Margaret; Samandari, Taraz; Chirenje, Zvavahera ; Elyanu, Peter J.; Makhema, Joseph; Kamuti, Ethel; Nuwagaba-Biribonwoha, Harriet; Badal-Faesen, Sharlaa; Brumskine, William; Coetzer, Soritha; Dawson, Rodney; Delany-Moretlwe, Sinead; Diacon, Andreas H.; Fry, Samantha; Gill, Katherine M.; Hoosain, Zaheer A. E.; Hosseinipour, Mina C.; Inambao, Mubiana; Innes, Craig; Innes, Steve; Kalonji, Dishiki; Kasaro, Margaret; Kassim, Priya; Kayange, Noel; Kilembe, William; Laher, Fatima; Malahleha, Moelo ; Maluleke, Vongane L.; Mboya, Grace; McHarry, Kirsten; Mitha, Essack; Mngadi, Kathryn ; Mda, Pamela; Moloantoa, Tumelo; Mutuluuza, Cissy K.; Naicker, Nivashnee; Naicker, Vimla; Nana, Anusha; Nanvubya, Annet; Nchabeleng, Maphoshane; Otieno, Walter; Potgieter, Elsje L.; Potloane, Disebo; Punt, Zelda; Said, Jamil; Singh, Yasmine; Tayob, Mohammed S.; Vahed, Yacoob; Wabwire, Deo O.; McElrath, Juliana M.; Kublin, James G.; Bekker, Linda-Gail ; Gilbert, Peter B.; Corey, Lawrence; Gray, Glenda E.; Huang, Yunda; Kotze, Philip
BACKGROUND: With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak. METHODS: Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. In a prospective cohort study design, we used covariate-adjusted Cox regression and counterfactual cumulative incidence methods to determine the hazard ratio and relative risk of COVID-19 and severe COVID-19 with hybrid versus vaccine immunity within six months. The ongoing Ubuntu study is registered on ClinicalTrials.gov (NCT05168813) and this work was conducted from December 2021 to March 2023. FINDINGS: Between December 2021 and September 2022, 14,237 participants enrolled, and 14,002 (83% PLWH, 69% SARS-CoV-2 seropositive) were included in the analyses. Vaccinations were safe and well tolerated. Common adverse events were pain or tenderness at the injection site (26.7%), headache (20.4%), and malaise (20.3%). Severe adverse events were rare (0.8% of participants after the first and 1.1% after the second vaccination), and none were life-threatening or fatal. Among PLWH, the median CD4 count was 635 cells/μl and 18.5% had HIV viraemia. The six-month cumulative incidences in the hybrid immunity and vaccine immunity groups were 2.02% (95% confidence interval [CI] 1.61-2.44) and 3.40% (95% CI 2.30-4.49) for COVID-19, and 0.048% (95% CI 0.00-0.10) and 0.32% (95% CI 0.59-0.63) for severe COVID-19. Among all PLWH the hybrid immunity group had a 42% lower hazard rate of COVID-19 (hazard ratio [HR] 0.58; 95% CI 0.44-0.77; p < 0.001) and a 73% lower hazard rate of severe COVID-19 (HR 0.27; 95% CI 0.07-1.04; p = 0.056) than the vaccine immunity group, but this effect was not seen among PLWH with CD4 counts <350 cells/μl or HIV viraemia. Twenty PLWH had persistent SARS-CoV-2 virus at least 50 days. INTERPRETATION: Hybrid immunity was associated with superior protection from COVID-19 compared to vaccine immunity with the ancestral mRNA-1273 vaccine. Persistent infections among immunocompromised PLWH may provide reservoirs for emerging variants. FUNDING: National Institute of Allergy and Infectious Diseases.
Neutralizing antibody responses over time in a demographically and clinically diverse cohort of individuals recovered from SARS-CoV-2 acquisition in Africa: A cohort study
(PLOS Global Public Health, 2025-09-11) Karuna, Shelly; Sue Li, Shuying; Grant, Shannon; Walsh, Stephen R.; Frank, Ian; Casapia, Martin; Trahey, Meg; Hyrien, Ollivier; Fisher, Leigh; Miner, Maurine D.; Randhawa, April K.; Polakowski, Laura; Kublin, James G.; Corey, Lawrence; Montefiori, David
Background: People infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) experience a wide range of clinical manifestations, from asymptomatic and mild illness to severe illness and death, influenced by age and a variety of comorbidities. Neutralizing antibodies (nAbs) are thought to be a primary immune defense against the virus. Large, diverse, well-characterized cohorts of convalescent individuals provide standardized values to benchmark nAb responses to past SARS-CoV-2 infection and define potentially protective levels of immunity. Methods and findings: This analysis comprises an observational cohort of 329 HIV-seronegative adults in the United States (n = 167) and Peru (n = 162) convalescing from SARS-CoV-2 infection from May through October 2020. The mean age was 48 years (range 18 to 86), 54% of the cohort overall was Hispanic, and 34% identified as White. nAb titers were measured in serum by SARS-CoV-2.D614G Spike-pseudotyped virus infection of 293T/ACE2 cells. Multiple linear regression was applied to define associations between nAb titers and demographic variables, disease severity and time from infection or disease onset, and comorbidities within and across US and Peruvian cohorts over time. nAb titers peaked 28 to 42 days post-diagnosis and were higher in participants with a history of severe Coronavirus Disease 2019 (COVID-19) (p < 0.001). Diabetes, age >55 years, male sex assigned at birth, and, in some cases, body mass index were also independently associated with higher nAb titers, whereas hypertension was independently associated with lower nAb titers. nAb titers did not differ by race, underlying pulmonary disease or smoking. Two months post-enrollment, nAb ID50 (ID80) titers declined 3.5 (2.8)-fold overall. Study limitations in this observational, convalescent cohort include survivorship bias and missing early viral loads and acute immune responses to correlate with the convalescent responses we observed. Conclusions: In summary, in our cohort, nAb titers after SARS-CoV-2 infection peaked approximately 1 month post-diagnosis and varied by age, sex assigned at birth, disease severity, and underlying comorbidities. Our data show great heterogeneity in nAb responses among people with recent COVID-19, highlighting the challenges of interpreting natural history studies and gauging responses to vaccines and therapeutics among people with recent infection. Our observations illuminate potential correlations of demographic and clinical characteristics with nAb responses, a key element for protection from COVID-19, thus informing development and implementation of preventative and therapeutic strategies globally.
Protein Dose-Sparing Effect of AS01B Adjuvant in a Randomized Preventive HIV Vaccine Trial of ALVAC-HIV (vCP2438) and Adjuvanted Bivalent Subtype C gp120.
(2024-Aug-16) Chirenje, Zvavahera M.; Laher, Fatima; Dintwe, One; Muyoyeta, Monde; deCamp, Allan C.; He, Zonglin; Grunenberg, Nicole; Laher, Faatima, O.; Seaton, Kelly E.; Polakowski, Laura; Davis, Amanda S. W.; Maganga, Lucas; Baden, Lindsey R.; Mayer, Kenneth; Kalams, Spyros ; Keefer, Michael; Edupuganti, Srilatha; Rodriguez, Benigno; Frank, Ian; Scott, Hyman; Stranix-Chibanda, Lynda; Gurunathan, Sanjay; Koutsoukos, Marguerite; Van Der Meeren, Olivier; DiazGranados, Carlos A.; Paez, Carmen; Andersen-Nissen, Erica; Kublin, James; Corey, Lawrence ; Ferrari, Guido; Tomaras, Georgia; McElrath, Juliana M.
BACKGROUND: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled human immunodeficiency virus (HIV) vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env protein at 2 dose levels in healthy HIV-uninfected adults. METHODS: Participants received ALVAC-HIV (vCP2438) alone or placebo at months 0 and 1. At months 3 and 6, participants received either placebo, ALVAC-HIV (vCP2438) with 200 μg of bivalent subtype C gp120 adjuvanted with MF59 or AS01B, or ALVAC-HIV (vCP2438) with 40 μg of bivalent subtype C gp120 adjuvanted with AS01B. Primary outcomes were safety and immune responses. RESULTS: We enrolled 160 participants, 55% women, 18-40 years old (median age 24 years) of whom 150 received vaccine and 10 placebo. Vaccines were generally safe and well tolerated. At months 6.5 and 12, CD4+ T-cell response rates and magnitudes were higher in the AS01B-adjuvanted groups than in the MF59-adjuvanted group. At month 12, HIV-specific Env-gp120 binding antibody response magnitudes in the 40 μg gp120/AS01B group were higher than in either of the 200 μg gp120 groups. CONCLUSIONS: The 40 μg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses. Clinical Trials Registration . NCT03122223.