Monoclonal antibodies: an untapped resource for global health

In the face of persistent and emerging public health threats, the global health community acknowledges the critical need for a diverse arsenal of medical countermeasures, including vaccines, diagnostics, drugs, and immune-based treatments such as monoclonal antibodies (mAbs), to address outbreaks swiftly and effectively. The latter, mAbs, have transformed modern medicine, offering hope against diseases like cancer and autoimmune disorders, yet mAb access remains limited, particularly in low- and middle-income countries (LMICs).

Image source: How monoclonal antibodies can help keep Mississippians out of the hospital, Kobee Vance

A joint report by Impact Global Health and IAVI examines the current state of R&D and access for monoclonal antibodies and related products (e.g. nanobodies), building on the 2020 global call to action by IAVI and Wellcome to improve mAbs access in LMICs. The report explores the global landscape of approved mAbs and biosimilars, with a focused analysis of the situation in Africa – the region with the fewest approved mAbs in 2020. It also highlights mAbs in development for diseases significantly affecting Africa, spanning both non-communicable diseases, such as cancer and autoimmune disorders, and infectious diseases.

This analysis takes a deep dive into mAbs R&D for infectious diseases, focusing on two of the deadliest human diseases, malaria and HIV/AIDS, which continue to pose a significant threat in many parts of the world, particularly in LMICs. Approximately 39 million people were living with HIV at the end of 2022 globally, of which over 600 000 people died from HIV-related causes in 2022, mostly in Africa. In 2022, about 249 million malaria cases and over 600,000 deaths were reported across 85 countries. Like HIV, the WHO African region was the most affected, accounting for 94% of cases and almost all deaths (95%). Children under 5 years of age represented around 80% of all malaria-related fatalities in the region.

Monoclonal antibodies are highly specific proteins developed in the laboratory as copies of antibodies that our own bodies produce to combat diseases. They can be used to either prevent or treat disease by mimicking naturally occurring antibodies – binding to harmful pathogens and signalling the immune system for a response, thereby enabling the human body to neutralise the offending agent.

Prior to the widespread use of antibiotics, antibodies taken from animals and people who had recovered from an infection were used to treat diseases like cholera and gonorrhoea. However, they were given in an unpurified form – primarily infusing patients with serum (serotherapy), resulting in patients receiving a mixture of various antibodies and other proteins. This caused many undesirable side effects - hypersensitivity reactions, predominantly allergic reactions, leading to a decrease in their use. Nonetheless, the confirmation of the protective efficacy of rabies immunoglobulins in 1954 represented a significant milestone in antibody administration during infections, heralding a medical breakthrough, especially in the clinical treatment of rabies, a practice that endures to this day.

With the discovery of monoclonal antibodies in the 1975, there was renewed interest in antibodies as medicines. In 1998, one of the first mAbs to be approved for an infectious disease was palivizumab to prevent the respiratory infection caused by the respiratory syncytial virus (RSV), although its use remains limited especially in LMICs. Recently, new RSV mAbs, which have better regimen profile, have been approved. For example, the new long acting mAb, nirsevimab, is given once to cover a 6-month RSV season rather than palivizumab which is given 5 times to provide the same level of protection. This reduced dose schedule also means it costs less so can be given to more children.

Over 100 mAbs have been approved or under consideration for approval worldwide, with only 11 for infectious diseases. Further exploration for other infections is ongoing due to recognised benefits:

• mAbs are customised to a targeted disease and offer a good safety profile with few side effects, alone or when combined with other treatments.
• They provide immediate protection and remain effective for extended periods, improving treatment adherence.
• Where possible, laboratory modifications can prolong their half-life and effects, a desirable characteristic for LMICs.

Practically, the development of COVID-19 mAbs demonstrated antibody development as an effective means of rapidly responding to emerging pathogens on a wider scale when vaccines are unavailable. The COVID-19 pandemic also brought to attention the significant challenges in large-scale mAb use including high costs, pathogen mutation leading to resistance, and market competition from less costly, available vaccines and drugs. Despite these hurdles, it is important to acknowledge that technological advances have improved mAb production, potency, and product half-life, increasing the potential for developing cheaper products for use in LMICs.

Decades of HIV antibody research resulted in the FDA-approved HIV mAb, Ibalizumab (IBA), for the treatment of HIV-1 infection in 2018. However, IBA is used with other antiretrovirals (ART) for heavily treatment-experienced adults with multidrug resistance, restricting its broader HIV treatment application. The global HIV burden demands continuous innovation that can provide durable, or at best, lifelong protection against HIV infection. Given this priority, preventative mAbs are sought for HIV protection. Broadly neutralising antibodies (bNAbs) show promise in long-acting HIV prevention, with potent activity against multiple strains and potential to provide longer duration of protection, reduce ART resistance and stigma.

The Antibody-Mediated Prevention (AMP) studies showed NIH’s VRC01 bNAb prevented the acquisition of susceptible HIV strains, but also indicated that multiple antibodies may be needed for better protection, like combination ART for HIV treatment. These findings have informed current antibody R&D strategies to develop a more effective HIV prevention therapy. Currently, multiple HIV mAbs are advancing through clinical development with noteworthy growth in Phase I candidates.

Recent WHO data shows stalled progress in malaria control with existing interventions. In recent years, there has been major progress in the malaria vaccine R&D, with two WHO-recommended vaccines. However, challenges with maintaining long-lasting protection from the vaccines exist. This remains a major limitation alongside the cost of development signalling the need for diverse effective tools like mAbs, alongside vaccines, to combat malaria.

Unlike vaccines, mAbs act immediately when administered and generate a less variable immune response. As such, mAbs can deliver immediate protection in high-risk populations. The simplified single dose regimen could potentially improve coverage and adherence. As a result of the promising benefits, malaria mAbs is an active R&D area being pursued. Currently, four malaria mAbs are being tested in clinical trials, with promising progress.

See our Infectious disease R&D tracker for more details on the HIV and malaria pipelines.

Funding for HIV/AIDS mAbs rose to a new peak of $49m in 2022 (up $14m, 38%), surpassing its previous 2019 peak, and sitting well above its yearly average of $24m. Moreover, malaria mAb funding more than tripled to $28m in 2022 (up $20m, 248%), following five consecutive years of steady growth. R&D for mAbs against HIV/AIDS and malaria relied heavily on the US NIH and philanthropic investment from the Gates Foundation.

Further in-depth analysis on funding trends is included in the latest report.

Despite decades of R&D on monoclonal antibodies (mAbs) for infectious diseases, progress has been hindered by high costs and limited understanding of the human-pathogen immunobiology. However, recent technological advancements offer hope, with G-FINDER data showing a rise in funding for both HIV and malaria mAb research. Still, there are glaring disparities in funding for these endemic diseases compared to epidemic diseases perceived as biosecurity threats in high-income countries. For instance, COVID-19 mAbs have received $1,167m since 2020, which is more than double the combined investments for HIV/AIDS and malaria since the start of our data collection in 2007 ($466m). Total mAb funding for Ebola since 2014 ($751m) also sits well above funding totals for HIV/AIDS ($406m) and malaria ($60m)-related mAbs research and development. This stark imbalance calls for renewed commitment to innovate against long-standing burdensome diseases. mAbs could play a pivotal role, alongside vaccines and other countermeasures based off their promising benefits. To unlock their potential, we need innovative actions to accelerate R&D efforts for effective, cost-efficient mAbs while dismantling access barriers. The time to act is now.