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Immune Complex Vaccine Strategies to Combat HIV-1 and Other Infectious Diseases.

ABSTRACT: Immune complexes (ICs) made of antibody-bound antigens exhibit immunomodulatory activities exploitable in a vaccination strategy to optimize vaccine efficacy. The modulatory effects of ICs are typically attributed to the Fc fragments of the antibody components, which engage Fc receptors, complement and complement receptors on various immune cells. These Fc-mediated functions facilitate the critical interplay between innate and adaptive immune systems to impact the quality and quantity of the elicited adaptive responses. In addition to the Fc contribution, the Fab fragment also plays an immunoregulation role. The antigen-binding domains of the Fab fragment can bind their specific epitopes at high affinity to sterically occlude these antigenic sites from recognition by other antibodies. Moreover, the Fab-mediated binding has been demonstrated to induce allosteric alterations at nearby or distant antigenic sites. In this review article, we survey published studies to illuminate how the immunomodulatory functions of ICs have been investigated or utilized in a vaccination strategy to fight against an array of infectious pathogens, culminating with IC vaccine designs aimed at preventing HIV-1 infection. In particular, we highlight IC vaccine candidates that exploit Fab-mediated steric and allosteric effects to direct antibody responses away or toward the V1V2 domain, the V3 loop, and other antigenic sites on the HIV-1 envelope gp120 glycoprotein. Like other HIV-1 vaccine approaches, the path for IC-based vaccines to reach the clinic faces major hurdles yet to be overcome; however, investigations into this vaccine strategy have provided insights into the multifaceted activities of antibodies beyond their conventional roles in the host defense against HIV-1 and other microbial pathogens.

SUBMITTER: Tang AF

PROVIDER: S-EPMC7913084 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Immune Complex Vaccine Strategies to Combat HIV-1 and Other Infectious Diseases.

Tang Alex F AF Enyindah-Asonye Gospel G Hioe Catarina E CE

Vaccines 20210202 2

Immune complexes (ICs) made of antibody-bound antigens exhibit immunomodulatory activities exploitable in a vaccination strategy to optimize vaccine efficacy. The modulatory effects of ICs are typically attributed to the Fc fragments of the antibody components, which engage Fc receptors, complement and complement receptors on various immune cells. These Fc-mediated functions facilitate the critical interplay between innate and adaptive immune systems to impact the quality and quantity of the eli ...[more]

PMID: 33540685

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Project description:Vaccine allocation strategies become crucial during vaccine shortages, especially in the face of potential outbreaks of new infectious diseases, as witnessed during the COVID-19 pandemic. To address this, a specialized compartmental model is created, which simulates an emerging infectious disease similar to COVID-19. This model divides the population into different age groups and is used to compare various vaccine prioritisation approaches, aiming to minimize the total number of fatalities. The model is an improvement upon previous ones as it incorporates essential behavioural factors and is adapted to account for the protective effects of vaccination against both disease infection and transmission. It takes into account human behaviors such as mask-wearing and social distancing by utilizing specific parameters related to self-protection, awareness levels, and the frequency of daily person-to-person interactions within each age group. Furthermore, a novel method for dynamic vaccine prioritisation was introduced in this study. This approach is model-independent and relies on the dynamic R number. It is the first time such a method has been developed, offering a decision-making approach that is not tied to any specific model. This innovation provides a flexible and adaptable strategy for determining vaccine priorities based on real-time data and the current state of the outbreak. Our findings reveal crucial insights into vaccine allocation strategies. When the daily rollout rates are fast (0.75% or higher) and children are eligible for vaccination, prioritising groups with high daily person-to-person interactions can lead to substantial reductions in total fatalities (up to approximately 40% lower). On the other hand, if rollout rates are slower and overall vaccination coverage is high, focusing on vaccinating elders emerges as the most effective strategy, resulting in up to approximately 10% fewer fatalities. However, the scenario changes significantly when children are not eligible for vaccination, as they constitute a highly interactive population group. In this case, the differences between priority strategies become smaller. With fast daily rollout rates, prioritisation based on interactions achieves only a 7% reduction in total fatalities, while a slower rollout with vaccination of elders first leads to an approximately 11% reduction in fatalities compared to the scenario where children are eligible for vaccination. The impact of behavioural parameters is equally critical. When the self-protection levels exercised by the population are low, it significantly affects the optimal vaccine prioritisation strategy to be followed, making it essential to consider behavioural factors in decision-making.

Dataset Information

Immune Complex Vaccine Strategies to Combat HIV-1 and Other Infectious Diseases.

Publications

Immune Complex Vaccine Strategies to Combat HIV-1 and Other Infectious Diseases.

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