Alum for the Ride

 

Darrell Irvine, PhD, Ragon Steering Committee Member and MIT Professor of Materials Science and Biological Engineering, has just published a paper in Nature Medicine showing a way to engineer an increased immune response to the vaccine adjuvant aluminum hydroxide, also known as alum, in an HIV vaccine given to animals. 

 

Adjuvants like alum are used to heighten the body’s response to antigens, the vaccine component that trains the immune system to recognize an infectious disease. This heightened response increases the immune system’s “memory” of the antigen, allowing the body to more quickly recognize and attack the disease the antigen comes from. In most vaccines, alum and the antigen are given together; however, they can quickly separate once in the body. This means alum’s immune-enhancing effects are not always optimal during the vaccination process. 

 

Here, Irvine and collaborators show that adding a molecule called phosphoserine to an HIV antigen allows the alum and antigen to bind together during vaccination. This keeps the antigen attached to alum during the entire immune response, which in turn greatly increases the immune response to the antigen. This results in increased production of HIV antibodies, which strengthens immune memory. Antibodies are the tools used by the immune system to recognize previously encountered diseases and initiate immune response. More antibodies in response to a vaccine means better protection.

 

However, HIV vaccines face special challenges. In response to HIV immunization, most of the antibodies made are binding antibodies. These antibodies bind to a site, or epitope, on HIV that is constantly mutating, and this initiates the immune response. As the virus mutates, the epitope changes and the antibody can no longer recognize it. Because HIV constantly mutates in the body, these antibodies become quickly outdated. Neutralizing antibodies (NAb) are antibodies that bind to an epitope which prevents the HIV virus from infecting a cell; they also initiate the immune response.

 

Irvine engineered the alum and antigen binding so that some of the rapidly mutating epitopes were hidden while stable epitopes, which mutate less often, remained exposed. Using this conformation, the production of NAbs against HIV increased 6.5-fold compared to a non-alum-bound vaccination. This changed the immune response to HIV away from mostly binding antibodies against rapidly mutating epitopes to one with a mix of antibodies, including NAbs against stable epitopes. Altogether, this vaccination method may help induce a more durable and effective response to HIV vaccination.

 

This simple change to the antigen-alum interaction allowed for increased production of specific antibodies, an important finding for rapidly mutating viruses like HIV and the flu. It also allows for increased efficacy of vaccines using engineering of reliable, FDA-approved adjuvants instead of the lengthy and expensive process of developing new ones.

 

This project was a part of collaboration of the Ragon Institute of Mass General, MIT, and Harvard; the La Jolla Institute for Immunology; Scripps Research; and the Koch Institute for Integrated Cancer Research at MIT

 

Moyer, T.J., Kato, Y., Abraham, W. et al. Engineered immunogen binding to alum adjuvant enhances humoral immunity. Nat Med (2020). https://doi.org/10.1038/s41591-020-0753-3

 

About the Ragon Institute

The Ragon Institute of Mass General, MIT, and Harvard was established in 2009 with a gift from the Phillip T. and Susan M. Ragon Foundation, creating a collaborative scientific mission among these institutions to harness the immune system to combat and cure human diseases. A primary focus of the institute has been to contribute to the development of an effective AIDS vaccine, to understanding mechanisms of immune control and immune failure, and to benefit patients. For more information about the Ragon Institute, visit www.ragoninstitute.org.

 

About La Jolla Institute for Immunology

The La Jolla Institute for Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, nonprofit research organization, the Institute has made numerous advances leading toward its goal: life without disease.

 

About Scripps Research

Scripps Research advances scientific understanding, educates the scientists of tomorrow and impacts human health across the globe. We are science changing life.

 

About the Koch Institute for Integrative Cancer Research at MIT

The Koch Institute for Integrative Cancer Research, a National Cancer Institute-designated Basic Cancer Research Center, is the hub of cancer research on the MIT campus. Bringing together biologists, chemists, engineers, computer scientists, clinicians, and others in a state-of-the-art facility, the Koch Institute offers fresh perspectives and interdisciplinary approaches to advancing the fight against cancer. Working within the vibrant MIT research community and with external collaborators, including NCI-designated clinical cancer centers and biotech/pharma partners, the Koch Institute is dedicated to developing novel insights into cancer, as well as new tools and technologies to better detect, treat, and prevent the disease. 

 

For more information about MIT’s Koch Institute, please visit https://ki.mit.edu/

 

Image courtesy of the NIAID.