Nicole Grunenberg
A5008375484- HIV Research and Treatment
- vaccines and immunoinformatics approaches
- HIV/AIDS Research and Interventions
- SARS-CoV-2 and COVID-19 Research
- Viral gastroenteritis research and epidemiology
- HIV/AIDS drug development and treatment
- Vaccine Coverage and Hesitancy
- Monoclonal and Polyclonal Antibodies Research
- Hepatitis B Virus Studies
- Hepatitis C virus research
- Immunotherapy and Immune Responses
- Virology and Viral Diseases
- Immune Cell Function and Interaction
- SARS-CoV-2 detection and testing
- Adolescent Sexual and Reproductive Health
- Urinary Bladder and Prostate Research
- Nausea and vomiting management
- Reproductive tract infections research
- Herpesvirus Infections and Treatments
- HIV, Drug Use, Sexual Risk
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- Cytokine Signaling Pathways and Interactions
- T-cell and B-cell Immunology
- Syphilis Diagnosis and Treatment
Fred Hutch Cancer Center
2015-2025
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2021-2025
Seattle University
2023
Cancer Research Center
2019-2021
Infectious Disease Research Institute
2019
University of Cape Town
2016
Kenya AIDS Vaccine Initiative
2016
Perinatal HIV Research Unit
2016
International AIDS Vaccine Initiative
2016
National Institute of Allergy and Infectious Diseases
2016
A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. canarypox–protein HIV regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection Thailand. An analogous using HIV-1 subtype C potent humoral and cellular responses a phase 1–2a trial South Africa. Efficacy data additional safety were needed for this larger population
Microbiota can mislead antibodies Unlike the response to many viral infections, most people do not produce capable of clearing HIV-1. Non-neutralizing that target HIV-1's envelope glycoprotein (Env) typically dominate response, which is generated by B cells cross-react with Env and intestinal microbiota. Williams et al. analyzed samples from individuals who had received a vaccine containing protein, including gp41 subunit. Most were non-neutralizing targeted gp41. The also reacted...
Background VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that active against a broad range of primary isolates in vitro and protects simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown be safe well tolerated after short-term administration humans; however, its clinical functional activity longer-term not previously assessed. Methods findings HIV Vaccine Trials Network (HVTN) 104 was designed evaluate the...
BackgroundModest efficacy was reported for the HIV vaccine tested in RV144 trial, which comprised a canarypox vector (ALVAC) and envelope (env) glycoprotein (gp120). These components were adapted to express HIV-1 antigens from strains circulating South Africa, adjuvant changed increase immunogenicity. Furthermore, 12-month immunisation added improve durability. In Vaccine Trials Network (HVTN) 100 we aimed assess this new regionally regimen advancement testing.MethodsHVTN is phase 1/2,...
We evaluated our SARS-CoV-2 prefusion spike recombinant protein vaccine (CoV2 preS dTM) with different adjuvants, unadjuvanted, and in a one-injection two-injection dosing schedule previous phase 1-2 study. Based on interim results from that study, we selected the AS03 adjuvant for further clinical development. However, lower than expected antibody responses, particularly older adults, higher reactogenicity after second vaccination were observed. In current safety immunogenicity of an...
Background: A prophylactic HIV-1 vaccine is a global health priority. Objective: To assess novel platform as regimen. Design: Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149) Setting: United States, East Africa, South Africa. Patients: Healthy adults without HIV infection. Intervention: 2 vaccines (adenovirus serotype 26 with an envelope insert [Ad26.EnvA] adenovirus 35...
In South Africans, the RV144 HIV vaccine regimen elicited robust immune responses that have been associated with efficacy.
Abstract Background The ALVAC/gp120 + MF59 vaccines in the HIV Vaccine Trials Network (HVTN) 702 efficacy trial did not prevent human immunodeficiency virus-1 (HIV-1) acquisition. Vaccine-matched immunological endpoints that were correlates of HIV-1 acquisition risk RV144 measured HVTN and evaluated as Methods Among 1893 female vaccinees, 60 HIV-1–seropositive cases matched seronegative noncases sampled. HIV-specific CD4+ T-cell binding antibody responses 2 weeks after fourth fifth...
HVTN 100 evaluated the safety and immunogenicity of an HIV subtype C pox-protein vaccine regimen, investigating a 12-month booster to extend vaccine-induced immune responses.A phase 1-2 randomized double-blind placebo-controlled trial enrolled 252 participants (210 vaccine/42 placebo; median age 23 years; 43% female) between 9 February 2015 26 May 2015. Vaccine recipients received ALVAC-HIV (vCP2438) alone at months 0 1 with bivalent gp120/MF59 3, 6, 12. Antibody (IgG, IgG3 binding,...
Mirabegron is a potent and selective β3-adrenoceptor agonist in development for treatment of overactive bladder.Mirabegron pharmacokinetics after single intravenous (i.v.) oral doses, absolute bioavailability (F), dose proportionality, sex differences tolerability were assessed 2 single-dose, open-label, randomized, parallel-group, cross-over studies healthy men (exploratory Study 1, n = 12) women (Study 2, 91).After dosing (25 - 150 mg), peak plasma concentrations attained ~ 4 h. Mean...
The monoclonal antibody VRC01 targets the CD4 binding site of human immunodeficiency virus (HIV)-1 envelope. In clinical study HVTN 104 (NCT02165267), 84 HIV-uninfected adults received multiple-dose intravenous (IV) (10, 20, 30 or 40 mg/kg) every 4 8 weeks subcutaneous (SC) (5 2 weeks, and were followed for 32 weeks. We conducted a population pharmacokinetics (popPK) analysis based on 1117 serum concentrations using 2-compartment PK model with first-order elimination; SC depot compartment...
The pox-protein regimen tested in the RV144 trial is only vaccine strategy demonstrated to prevent HIV-1 infection. Subsequent analyses identified antibody and cellular immune responses as correlates of risk (CoRs) for HIV Early predictors these CoRs could provide insight into vaccine-induced protection guide efforts enhance efficacy. Using specimens from a phase 1b HIV-1-uninfected South Africans (HVTN 097), we profiled innate first ALVAC-HIV immunization. PBMC transcriptional peaked 1 day...
There is limited data about bacterial STIs in MSM populations sub-Saharan Africa. Our retrospective analysis used from the HVTN 702 HIV vaccine clinical trial (October 2016 to July 2021). We evaluated multiple variables. Polymerase chain reaction testing was conducted on urine and rectal samples detect Neisseria gonorrhoea (NG) Chlamydia trachomatis (CT) every 6 months. Syphilis serology at month 0 thereafter 12 calculated STI prevalence associated 95% confidence intervals until 24 months of...
Abstract Background HIV-1 vaccine development is a global health priority. Broadly neutralizing antibodies (bnAbs) which target the gp41 membrane-proximal external region (MPER) have some of highest neutralization breadth. An MPER peptide-liposome has been found to expand bnAb precursors in monkeys. Methods The HVTN133 phase 1 clinical trial ( NCT03934541 ) studied MPER-peptide liposome immunogen 24 seronegative individuals. Participants were recruited between 15 July 2019 and 18 October...
Background Adjuvants are widely used to enhance and/or direct vaccine-induced immune responses yet rarely evaluated head-to-head. Our trial directly compared elicited by MF59 versus alum adjuvants in the RV144-like HIV vaccine regimen modified for Southern African region. The RV144 of a recombinant canarypox vector expressing env subtype B (ALVAC-HIV) prime followed ALVAC-HIV plus bivalent gp120 protein boost adjuvanted with is only have shown modest efficacy. Data generated after suggested...
Background A phase 1 trial of a clade B HIV vaccine in HIV-uninfected adults evaluated the safety and immunogenicity DNA prime co-expressing GM-CSF (Dg) followed by different numbers intervals modified vaccinia Ankara Boosts (M). Both vaccines produce virus-like particles presenting membrane-bound Env. Methods Four US sites randomized 48 participants to receiving 1/10th dose as DgDgMMM given at 0, 2, 4, 6 8 months, or full DgDgM_M DgDgMM_M regimens, 6, 10 respectively. Peak was measured 2...
Background. VRC01, a potent, broadly neutralizing monoclonal antibody, inhibits simian-HIV infection in animal models. The HVTN 104 study assessed the safety and pharmacokinetics of VRC01 humans. We extend clinical evaluation to determine intravenously infused distribution protective function at mucosal sites HIV-1 entry.
BackgroundElicitation of broad immune responses is understood to be required for an efficacious preventative HIV vaccine. This Phase 1 randomized controlled trial evaluated whether administration vaccine antigens separated at multiple injection sites vs combined, fractional delivery affected T-cell breadth compared standard, single site vaccination.MethodsWe 90 participants receive recombinant adenovirus 5 (rAd5) vector with inserts gag, pol and env via three different strategies. The...
An effective vaccine is required to end the HIV pandemic. We evaluated safety and immunogenicity of a DNA (DNA-HIV-PT123) with low- or high-dose bivalent (TV1.C 1086.C glycoprotein 120) subtype C envelope protein combinations, adjuvanted MF59 AS01B.
Developing an effective HIV vaccine is a momentous challenge. An exceptionally wide range of candidate vaccines have been tested, yet many were poorly immunogenic, and the select few that advanced into efficacy trials, only one demonstrated any efficacy. Here we report results largest-scale cross-protocol immunogenicity comparison to date: 13 trials (including 36 regimens) conducted across nine countries worldwide, strengthened by standardized trial designs, validated assays in centralized...
Clostridium difficile is the leading cause of hospital-acquired infectious diarrhea. LFF571 a novel inhibitor prokaryotic translation elongation factor Tu and active against range bacterial species, including C. difficile. This first-in-human study investigated safety pharmacokinetics single multiple ascending oral doses in healthy subjects. was randomized, double-blind, placebo-controlled study. Except for one cohort, given with high-fat meal to all single-dose cohorts (25 mg, 100 400 1,000...
Abstract In the RV144 trial, vaccine-induced V1V2 IgG correlated with decreased HIV-1 risk. We investigated circulating antibody specificities in two phase 1 poxvirus prime-protein boost clinical trials conducted South Africa: HVTN 097 (subtype B/E) and 100 C). With cross-subtype peptide microarrays multiplex binding assays, we probed magnitude breadth of responses to linear variable loop 2 (V2) conformational specificities. Antibodies targeting V2 epitope, a correlate risk RV144, were...
Abstract Background COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern. Methods We conducted a global Phase 3, multi-stage efficacy study ( NCT04904549 ) among adults aged ≥18 years. Participants were randomized 1:1 receive two intramuscular injections 21 days apart bivalent recombinant protein vaccine AS03-adjuvant (5 μg ancestral (D614) and 5 B.1.351 [beta] variant spike protein) or placebo....