Sponsored Insight
Vaccines are undeniably considered one of the most important advancements in the history of modern medicine.1 While vaccines offer protection against serious infectious diseases, that protection is contingent upon the individual’s ability to mount a robust immune response. The most vulnerable among our society, like the immunocompromised, the very young and the elderly, may have a weakened response to vaccination. This leaves them insufficiently protected and facing a much higher chance of serious outcomes from infectious diseases2-4 —inspiring many scientists, myself included, to pursue alternative solutions for protection. Passive immunization, or the direct administration of infection-fighting monoclonal antibodies (mAbs), can offer rapid protection for vulnerable groups who may have an inadequate response to vaccination or need additional protection from infectious diseases.5,6
An approach to protect the most vulnerable
As we’ve learned, vulnerable populations may have an underdeveloped or weakened immune system, whether due to age, disease or immunosuppressive treatment, and may be significantly more susceptible to viral or bacterial infections, compared to healthy populations.2-4 For example, one study found that, despite being fully vaccinated and representing only about 4% of the population, immunocompromised individuals account for approximately 25% of COVID-19 hospitalizations, intensive care admissions and deaths in England.7 This population deserves effective preventative measures as much as everyone else—not to be forgotten in an unlucky healthcare gap.
The concept of passive immunization is a simple one: we administer infection-fighting antibodies directly to the right people. Over the past century, various passive immunization strategies have been used to successfully prevent diphtheria infections, hepatitis B infections in newborns, respiratory syncytial virus (RSV) infections in high-risk infants and COVID-19 infections in the immunocompromised.5,8,9 We have seen an impact on public health with the broad and rapid uptake of passive immunization strategies. One clear recent example is the use of passive immunization for RSV in a broad infant population, which shows up to 90% effectiveness in preventing hospitalizations when used to protect infants against RSV in their first RSV season.10
I am energized by these successes and the potential broader benefit to society. We are beginning to see an uptick in mAbs being investigated for the prevention of infectious disease, including Ebola, malaria, Staphylococcus aureus and Zika.9 The time to further explore the promise of mAbs for the prevention of a wide range of infectious diseases is now.
Scientific innovation in a field poised for expansion
Passive immunization using mAbs has the potential to offer vulnerable infants and adults long-lasting immunity against an array of viral and bacterial pathogens. At AstraZeneca, we are leaning into our deep experience and heritage in vaccines and immune therapies to help advance research in this space. Our scientists’ efforts include novel engineered antibodies with the capability to provide an extended duration of protection compared to traditional mAbs.
We are also working to make the development of mAbs as adaptable and efficient as possible to rapidly address viral pathogens as they arise. This includes investigation of a range of innovative approaches that deliver medicines faster and in a cost-effective manner. One notable example is our team using artificial intelligence to rapidly design antibodies to bind to new variants, allowing us to select the most promising molecules quickly in the face of a rapidly mutating virus.
A case for accelerating research and access
As scientific understanding and capabilities advance, so must the systems we put in place to make these technologies accessible to patients. Passive immunization has to be supported by flexible, tailored access frameworks and applied appropriately within clinical care standards. We need to create a sustainable mAb model in which innovation and adaptability access are championed.
A key challenge for infectious disease therapies is ensuring they can be developed and deployed quickly when needed. Many of us have experienced the duration and demands of traditional regulatory approval pathways first-hand. Alternative approaches, such as immunobridging, could greatly facilitate the development of mAbs for protection against infectious diseases and enable more expedient access. An immunobridging approach allows for efficacy of a product to be inferred based on achieving neutralizing antibody titers or other relevant immune measures correlated with protection.11 This type of approach has been successfully utilized to support use of vaccines in new populations following an initial demonstration of efficacy.11 It is a strong example of a system that has adapted to meet the evolving needs of patients. We must consider a flexible immunobridging approach for passive immunization mAbs against seasonally variable viruses, enabling a fast response time and rapid access for the immunocompromised.
Finally, it’s essential to identify appropriate patients. The intent of passive immunity with mAbs is not to serve as an additional layer of protection for society, but rather to be integrated into the care of those at high risk. The option must be included within clinical care pathways of vulnerable patients, requiring support and education for both healthcare providers and patients.
Looking to the future
Championing passive immunization through mAbs will continue to be my priority at AstraZeneca. We need to continue learning from past experiences with passive immunization and adapting the strategies we are using to address the problems of modern times. I’m inspired by the innovations seen throughout the world, and I encourage every scientist, researcher and physician to seize the opportunity to help protect vulnerable populations.
Learn more about AstraZeneca’s ambition to create a world where whole populations are protected against infectious diseases.
References
1. Amanna IJ, Slifka MK. Successful Vaccines. Curr Top Microbiol Immunol. 2020;428:1-30.
2. Centers for Disease Control and Prevention. Respiratory Viruses and People with Weakened Immune Systems. https://www.cdc.gov/respiratory-viruses/risk-factors/weakened-immune-systems.html [Last accessed: April 2024]
3. Centers for Disease Control and Prevention. Respiratory Viruses and Older Adults. https://www.cdc.gov/respiratory-viruses/risk-factors/older-adults.html [Last accessed: April 2024]
4. Centers for Disease Control and Prevention. Respiratory Viruses and Young Children. https://www.cdc.gov/respiratory-viruses/risk-factors/young-children.html [Last accessed: April 2024]
5. Slifka MK, Amanna IJ. Passive Immunization. Plotkin’s Vaccines. 2018:84–95.e10
6. Centers for Disease Control and Prevention Immunity Types. Published online 2021. https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm [Last accessed: April 2024]
7. Evans RA, Dube S, Lu Y, et al. Impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study. Lancet Reg Health Eur. 2023 Oct 13;35:100747.
8. Zeitlin L, Cone RA. Special focus issue: passive immunization. Hum Vaccin Immunother. 2022 Apr 29;18(2):2028517.
9. World Health Organization. Monoclonal Antibodies (mAbs) for Infectious Diseases. https://www.who.int/teams/immunization-vaccines-and-biologicals/product-and-delivery-research/monoclonal-antibodies-(mabs)-for-infectious-diseases. [Last accessed: April 2024]
10. Moline HL, Tannis A, Toepfer AP, et al. Early Estimate of Nirsevimab Effectiveness for Prevention of Respiratory Syncytial Virus-Associated Hospitalization Among Infants Entering Their First Respiratory Syncytial Virus Season – New Vaccine Surveillance Network, October 2023-February 2024. MMWR Morb Mortal Wkly Rep. 2024 Mar 7;73(9):209-214.
11. Fink D. Immunobridging to Evaluate Vaccines. https://cdn.who.int/media/docs/default-source/blue-print/doran-fink_4_immunobridging_vrconsultation_6.12.2021.pdf [Last accessed: April 2024]
Veeva ID: Z4-63365
Date of preparation: April 2024