Broadly neutralizing antibodies for HIV-1: efficacies, challenges and opportunities

Liu, Yubin; Cao, Wei; Sun, Ming; Li, Taisheng

doi:10.1080/22221751.2020.1713707

Cited by 64 publications

(50 citation statements)

References 87 publications

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“…HIV-1-specific broadly neutralizing antibodies (bNAbs) may be a key player as an “add-on” agent for HIV prevention, treatment, and perhaps, eradication [ 39 ].…”

Section: Bnabsmentioning

confidence: 99%

Injectable Antiretroviral Drugs: Back to the Future

Berruti

Riccardi

Canetti

et al. 2021

Viruses

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Current HIV treatment regimens provide sustained virologic suppression, at least partially restore the immune system and have limited side effects; however, they do not allow viral eradication and they are burdened by daily pill intake with a life-long commitment for the people living with HIV (PHIV). Injectable agents might represent a turning point in the care of PHIV, allowing less frequent administration of antiretroviral treatment (ART), more widespread use of pre-exposure prophylaxis (PrEP) and more stable drug levels in the blood, thus increasing the odds to get closer to end the HIV pandemic. The aim of this manuscript is to give a comprehensive review of injectable antiretrovirals that have been used in the past, which are available now, will be available in the future, and their role in the treatment of HIV infection

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“…HIV-1-specific broadly neutralizing antibodies (bNAbs) may be a key player as an “add-on” agent for HIV prevention, treatment, and perhaps, eradication [ 39 ].…”

Section: Bnabsmentioning

confidence: 99%

Injectable Antiretroviral Drugs: Back to the Future

Berruti

Riccardi

Canetti

et al. 2021

Viruses

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“…Following the encouraging results of preclinical studies, bnAbs have entered clinical trials for the prevention and treatment of HIV-1 infection. Antibodies against the CD4 binding site of HIV Env, VRC01, 3BNC117, VRC01-LS and VRC07-523LS, as well as antibodies targeting the glycan-rich V3 loop epitope, 10–1074 and PGT121, are being tested in humans [ 46 ]. The most advanced bnAb, the CD4-binding VRC01, is also being evaluated in Antibody Mediated Prevention (AMP) studies (NCT02716675, NCT02568215), to assessing its protective effect in individuals at high risk of HIV infection [ 47 ].…”

Section: Rsvmentioning

confidence: 99%

“…Despite their potential as valid treatment option to protect from or treat HIV infection, passive immunization with bnAbs faces critical challenges: suppression of viremia appears to be transient, with the virus readily escaping due to its high mutation rate, and the virus reservoir waiting quiescently in the host cells appear to be difficult to target. For this reason, a cocktail of modified, half-life extended bnAbs that targets different epitopes will certainly be required for HIV treatment, to avoid breakthroughs of resistant viral variants [ 46 , 48 ].…”

Section: Rsvmentioning

confidence: 99%

Quantum leap of monoclonal antibody (mAb) discovery and development in the COVID-19 era

Pecetta¹,

Finco²,

Seubert³

2020

Seminars in Immunology

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In recent years the global market for monoclonal antibodies (mAbs) became a multi-billion-dollar business. This success is mainly driven by treatments in the oncology and autoimmune space. Instead, development of effective mAbs against infectious diseases has been lagging behind. For years the high production cost and limited efficacy have blocked broader application of mAbs in the infectious disease space, which instead has been dominated for almost a century by effective and cheap antibiotics and vaccines. Only very few mAbs against RSV, anthrax, Clostridium difficile or rabies have reached the market. This is about to change. The development of urgently needed and highly effective mAbs as preventive and therapeutic treatments against a variety of pathogens is gaining traction. Vast advances in mAb isolation, engineering and production have entirely shifted the cost-efficacy balance. MAbs against devastating diseases like Ebola, HIV and other complex pathogens are now within reach. This trend is further accelerated by ongoing or imminent health crises like COVID-19 and antimicrobial resistance (AMR), where antibodies could be the last resort. In this review we will retrace the history of antibodies from the times of serum therapy to modern mAbs and lay out how the current run for effective treatments against COVID-19 will lead to a quantum leap in scientific, technological and health care system innovation around mAb treatments for infectious diseases.

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“…An important advantage revealed by some of these studies of infectious disease prophylaxis, but with relevance to other disease indications that may benefit from mAb combination therapy (such as trastuzumab with pertuzumab for HER2+ breast cancer), is the relative ease of delivering multiple mAbs by DNA/EP. For some infectious diseases, such as HIV-1, a number of broadly reactive and very potent NAbs have been identified, so-called broadly neutralizing antibodies (bNAbs), which have the potential to single-handedly prevent or treat infection by a wide range of virus strains (Figure 3) [66,67]. Even these remarkable molecules, however, work most effectively in combination, particularly as a means to reducing the emergence of resistant viruses.…”

Section: Main Textmentioning

confidence: 99%

In vivo expressed biologics for infectious disease prophylaxis: rapid delivery of DNA-based antiviral antibodies

Andrews

Huang

et al. 2020

Emerging Microbes & Infections

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With increasing frequency, humans are facing outbreaks of emerging infectious diseases (EIDs) with the potential to cause significant morbidity and mortality. In the most extreme instances, such outbreaks can become pandemics, as we are now witnessing with COVID-19. According to the World Health Organization, this new disease, caused by the novel coronavirus SARS-CoV-2, has already infected more than 10 million people worldwide and led to 499,913 deaths as of 29 June, 2020. How high these numbers will eventually go depends on many factors, including policies on travel and movement, availability of medical support, and, because there is no vaccine or highly effective treatment, the pace of biomedical research. Other than an approved antiviral drug that can be repurposed, monoclonal antibodies (mAbs) hold the most promise for providing a stopgap measure to lessen the impact of an outbreak while vaccines are in development. Technical advances in mAb identification, combined with the flexibility and clinical experience of mAbs in general, make them ideal candidates for rapid deployment. Furthermore, the development of mAb cocktails can provide a faster route to developing a robust medical intervention than searching for a single, outstanding mAb. In addition, mAbs are well-suited for integration into platform technologies for delivery, in which minimal components need to be changed in order to be redirected against a novel pathogen. In particular, utilizing the manufacturing and logistical benefits of DNA-based platform technologies in order to deliver one or more antiviral mAbs has the potential to revolutionize EID responses.

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Broadly neutralizing antibodies for HIV-1: efficacies, challenges and opportunities

Cited by 64 publications

References 87 publications

Injectable Antiretroviral Drugs: Back to the Future

Injectable Antiretroviral Drugs: Back to the Future

Quantum leap of monoclonal antibody (mAb) discovery and development in the COVID-19 era

In vivo expressed biologics for infectious disease prophylaxis: rapid delivery of DNA-based antiviral antibodies

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