CROI 2024 Abstract eBook

Abstract eBook

Invited Session

into phase 1 clinical trials (NCT03547245, NCT05471076, NCT04224701). The emerging data from these trials, showing the effective priming of VRC01-class B cells in humans, provide proof of concept that the germline-targeting approach holds much promise. The challenges ahead include the further maturation of these VRC01-class B cells by 'shaping' and 'polishing' immunogens to generate bNAbs. Second, the strategy must be applied to other epitopes as an effective vaccine will likely require the induction of bNAbs against multiple epitopes. New developments in mRNA technology, adjuvant technology, and AI-based immunogen design will accelerate developing germline-targeting vaccination approaches that yield bNAbs. Novel Immunization Strategies to Move on Down the Road Darrell Irvine Massachusetts Institute of Technology, Cambridge, MA, USA Background: Progress is being made in the development of HIV Env immunogens with the potential to activate and expand B cell precursors capable of maturing to produce broadly neutralizing antibodies (bnAbs) that could protect against HIV infection. However, such precursors are generally very rare in the human B cell repertoire and must make challenging sets of mutations in their antigen receptors (via somatic hypermutation in germinal centers, GCs) in order to produce bnAbs. In addition, once expanded and matured, these B cells must be driven to differentiate into long-lived plasma cells that can produce high levels of protective circulating antibodies and provide long-lasting protection. These immunological challenges to the development of an HIV vaccine are being tackled by a variety of approaches to formulate engineering vaccine immunogens in a manner that can optimally stimulate the B cell response, amplify GC responses, and promote high titers of output antibody production. This talk will summarize recent advances in the design of nanoparticle immunogens, vaccine dosing schedules that augment the GC response, potent new adjuvants in development, and the use of new vaccine technologies such as mRNA to promote the humoral immune response. Epidemiology of Perinatally Acquired HIV Among Adolescents and Young Adults Mutsawashe Bwakura-Dangarembizi University of Zimbabwe, Harare, Zimbabwe Background: Adolescents (10–19 years) and youth (15–24 years) living with perinatally acquired HIV represent increasing proportions of people living with HIV. Improved access to antiretroviral therapy globally has resulted in children who acquire HIV around the time of birth or through breastfeeding surviving into adolescence. While many are thriving, a significant proportion face several challenges that can affect their long-term outcomes. In particular, poorly controlled HIV disease resulting from suboptimal early regimens and nonadherence, together with the toxicities of some ARV drugs, can predispose them to long-term sequelae including HIV-associated complications and other comorbidities. This talk will be focusing on the state of the epidemic, the global epidemiology and trends of perinatally acquired HIV among adolescents over the years in the different geographical locations. acquired HIV experience poorer HIV-related outcomes compared to younger children and adults with HIV, dying more often and experiencing greater challenges in terms of treatment adherence and staying in care. Historic Evolution of HIV and Mental Well-Being Among Adults Living With Perinatally Acquired HIV Ezer Kang Howard University, Washington, DC, USA Background: Adults living with perinatally acquired HIV (PHIV) in the United States (US) have experienced key historic epochs of an epidemic since the 1990s. They navigated four lifespan periods – childhood, adolescence, young adulthood, and adulthood - spanning over three decades of the HIV epidemic. This has indelibly shaped the contours of their development and mental health. Influenced by a "complex interplay of individual, social and structural stresses and vulnerabilities" (World Health Organization, 2022), mental health is not merely the absence of mental disorder – it is a state of mental well-being. This paper explores three dimensions of mental well-being – emotional, psychological, and social (Westerhof & Keyes, 2010) - among Black adults living with PHIV in the US, with a focus on their formation in concert with two historic markers – treatment innovation and illness stigma. Drawing from a qualitative study of 20 Black adults living with PHIV in New York City and a select review of the history of pediatric HIV in the US, three dialectic themes will be presented

Recent breakthroughs in understanding how broadly neutralizing antibodies interact with their target epitopes on the HIV envelope spike have led to new HIV envelope immunogen designs that may over time provide a path to eliciting these types of antibodies. Also, novel vaccine designs for inducing highly functional CD8+ T cells with antiviral activities. By leveraging new vaccine technologies and delivery systems, and tailored trial designs, we aim to speed up the pace of progress. Shall We Reach Human Papillomavirus Elimination in the Face of Inequity? Nelly R Mugo Kenya Medical Research Institute, Nairobi, Kenya Background: In the 1950s discovery and implementation of the 'Papsmear' was a game changer and saved millions of women from cervical cancer deaths. Seven decades later, 342,000 women die annually from cervical cancer, the most common human papilloma virus (HPV) infection associated cancer. The scientific world has made great strides in discovery and there is unequivocal scientific evidence of highly effective interventions to prevent, diagnose, and treat human papilloma virus associated diseases. The discovery of a highly effective prophylactic HPV vaccines, sensitive screening and effective treatment interventions led to the 2018 World Health Organization (WHO) call for Global elimination of cervical cancer, a disease almost entirely caused by high risk (hr) HPV infection. An effective vaccine has reduced HPV related morbidities across gender. Countries that have effectively implemented HPV vaccine and screening for pre-cancer lesions have met the threshold for elimination. Global variance in disease burden reflects inequity in access to health care services and challenges in implementation, and countries with high disease burden have low coverage to interventions. HPV self sampling, evidence and adoptation of single dose HPV vaccine are part of innovative strategies to increase uptake of effective interventions. The science world continuous to seek innovative interventions to close the gap to access to effective interventions, with efforts toward therapeutic HPV vaccine, medical therapy for pre-cancer lesions and implementation science. Is Global elimination for HPV infection feasible and does the world have what it takes to make it a Global reality? Neutralizing Antibody Protection: Where Do We Go From Here? Yunda Huang Fred Hutchinson Cancer Center, Seattle, WA, USA Background: The Antibody Mediated Prevention (AMP) trials did not demonstrate HIV prevention efficacy (PE) of the CD4-binding-site-targetting broadly neutralizing antibody (bnAb), VRC01 (10mg/kg or 30mg/kg IV vs. placebo). However, 75% PE was observed against viruses sensitive to VRC01 with an IC 80 200 at the estimated time of exposure to a given exposing virus was associated with high PE, validating in humans consistent patterns observed in non-human primate (NHP) challenge studies of different single bnAbs. This knowledge can be applied to predict PE of combinations of long-acting LS modified bnAbs targeting non-overlapping HIV epitopes. As with combination anti-retroviral-therapy for HIV treatment, combination bnAbs may overcome neutralization resistance and provide more potent coverage for HIV prevention. Background: It is generally believed that an HIV-1 vaccine should induce broadly neutralizing antibodies (bNAbs), but no vaccine candidate so far has been able to do so effectively. A critical step in the generation of HIV-1 bNAbs is the activation of specific naïve B cells expressing germline antibody precursors that have the potential to evolve into bNAbs. However, envelope glycoprotein (Env) vaccine candidates are generally unable to do so unless specifically modified. Initial germline-targeting vaccine design approaches have focused on VRC01-class B cells named after the first known bNAb of this class. VRC01-class B cells are attractive targets for germline targeting the following reasons: 1) the AMP trial showed that when present at high titer, VRC01 can protect humans from HIV-1 acquisition; 2) VRC01-class bNAbs have been isolated from multiple HIV-1 infected individuals indicating that the human immune system can reproducibly generate such bNAbs; 3) they target the conserved CD4 binding site on HIV-1 Env, limiting the opportunities for viral escape and 4) they have a very specific and distinct genetic signature (a heavy chain derived from VH1-2 combined with a light chain with an unusually short 5 amino acid CDRL3). Three VRC01-class germline-targeting 'priming' vaccine candidates have moved Germline Targeting Strategies to Get On the Road Again Rogier W Sanders Academic Medical Center, Amsterdam, Netherlands

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CROI 2024