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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:ObjectiveTo assess the costs and health effects of a range of interventions for preventing the spread of HIV and for treating people with HIV/AIDS in the context of the millennium development goal for combating HIV/AIDS.DesignCost effectiveness analysis based on an epidemiological model.SettingAnalyses undertaken for two regions classified using the WHO epidemiological grouping-Afr-E, countries in sub-Saharan Africa with very high adult and high child mortality, and Sear-D, countries in South East Asia with high adult and high child mortality.Data sourcesBiological and behavioural parameters from clinical and observational studies and population based surveys. Intervention effects and resource inputs based on published reports, expert opinion, and the WHO-CHOICE database.Main outcome measuresCosts per disability adjusted life year (DALY) averted in 2000 international dollars (Int dollars).ResultsIn both regions interventions focused on mass media, education and treatment of sexually transmitted infections for female sex workers, and treatment of sexually transmitted infections in the general population cost < Int150 dollars per DALY averted. Voluntary counselling and testing costs < Int350 dollars per DALY averted in both regions, while prevention of mother to child transmission costs < Int50 dollars per DALY averted in Afr-E but around Int850 dollars per DALY in Sear-D. School based education strategies and various antiretroviral treatment strategies cost between Int500 dollars and Int5000 dollars per DALY averted.ConclusionsReducing HIV transmission could be done most efficiently through mass media campaigns, interventions for sex workers and treatment of sexually transmitted infections where resources are most scarce. However, prevention of mother to child transmission, voluntary counselling and testing, and school based education would yield further health gains at higher budget levels and would be regarded as cost effective or highly cost effective based on standard international benchmarks. Antiretroviral therapy is at least as cost effective in improving population health as some of these interventions.

Project description:There is growing concern in Sub-Saharan Africa about the spread of the Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, and the public health burden that it ensues. Since 1976, there have been 885,343 suspected and laboratory confirmed cases of EVD and the disease has claimed 2,512 cases and 932 fatality in West Africa. There are certain requirements that must be met when responding to EVD outbreaks and this process could incur certain challenges. For the purposes of this paper, five have been identified: (i) the deficiency in the development and implementation of surveillance response systems against Ebola and others infectious disease outbreaks in Africa; (ii) the lack of education and knowledge resulting in an EVD outbreak triggering panic, anxiety, psychosocial trauma, isolation and dignity impounding, stigmatisation, community ostracism and resistance to associated socio-ecological and public health consequences; (iii) limited financial resources, human technical capacity and weak community and national health system operational plans for prevention and control responses, practices and management; (iv) inadequate leadership and coordination; and (v) the lack of development of new strategies, tools and approaches, such as improved diagnostics and novel therapies including vaccines which can assist in preventing, controlling and containing Ebola outbreaks as well as the spread of the disease. Hence, there is an urgent need to develop and implement an active early warning alert and surveillance response system for outbreak response and control of emerging infectious diseases. Understanding the unending risks of transmission dynamics and resurgence is essential in implementing rapid effective response interventions tailored to specific local settings and contexts.(i) national and regional inter-sectorial and trans-disciplinary surveillance response systems that include early warnings, as well as critical human resources development, must be quickly adopted by allied ministries and organisations in African countries in epidemic and pandemic responses; (ii) harnessing all stakeholders commitment and advocacy in sustained funding, collaboration, communication and networking including community participation to enhance a coordinated responses, as well as tracking and prompt case management to combat challenges; (iii) more research and development in new drug discovery and vaccines; and (iv) understanding the involvement of global health to promote the establishment of public health surveillance response systems with functions of early warning, as well as monitoring and evaluation in upholding research-action programmes and innovative interventions.

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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