New Adjuvant Boosts SARS-CoV-2 Protection in Mice

By Marilynn Larkin

March 05, 2021

NEW YORK (Reuters Health) - A novel adjuvant that delivered a SARS-CoV-2 vaccine directly to the lymph nodes in mice might be an effective option for humans, researchers suggest.

"Our new vaccine adjuvant, Amphiphile (AMP)-CpG is exciting because it can 'hitchhike' on albumin from the site of injection and ride into lymph nodes where new T cell and B cell responses begin," Dr. Christopher Haqq of Elicio Therapeutics in Cambridge, Massachusetts, which funded the study and employs all the authors. "Having a way to target new variants through T cells could make a huge difference in the pandemic."

"Our (study) showed that AMP-CpG with the SARS-CoV-2 receptor binding domain generated 25-fold higher numbers of T cells compared to standard vaccine adjuvants," he noted. "We found T cells not only in the peripheral blood, but also in lung tissue, and even in the respiratory fluid that would be the first site to be infected if a patient developed COVID-19 pneumonia."

As reported in Science Advances, Dr. Haqq and colleagues evaluated an AMP-CpG adjuvant made of diacyl lipid-modified cytosine-guanine (CpG) admixed with the SARS-CoV-2 Spike-2 receptor binding domain protein as a candidate vaccine (ELI-005) in mice.

As Dr. Haqq indicated, the adjuvant efficiently delivered CpG to lymph nodes, where innate and adaptive immune responses are generated. Mice immunized with a vaccine containing the new adjuvant had an antigen-specific T-cell response that was more than 25-fold greater than that of mice given the same vaccine with alum; importantly, as Dr. Haqq noted, the T cells also traveled to the lungs.

In another experiment, the team tested a vaccine containing AMP-CpG admixed with the SARS-CoV-2 spike receptor (Spike RBD) at varying doses (1, 5, and 10 micrograms). Even the 1-microgram antigen admixed with AMP-CpG yielded a significantly higher T cell response than CpG-only or alum mixed with a 10-microgram antigen dose.

Further, the antibody responses favored TH1 isotypes (IgG2c and IgG3), and neutralized SARS-CoV-2 with titers 265-fold higher than antibodies naturally present in convalescent patient COVID-19 responses; T cell and antibody responses were maintained even with the 10-fold dose reduction in Spike antigen.

"We also tested a group of aged mice that have impaired immune responses to model elderly humans like nursing home populations," Dr. Haqq said. "Despite the decline in the immune system that occurs with aging, we saw potent responses similar to young mice."

The authors conclude that the adjuvant "merit(s) clinical translation to SARS-CoV-2 and other protein subunit vaccines."

Dr. Haqq added, "AMP-CpG is not only part of our SARS-CoV-2 vaccine candidate, it is also the key adjuvant in our company's lead oncology product candidate, ELI-002, which targets mutant forms of KRAS, found in many solid tumors. We've just received FDA clearance to begin our cancer trial, so we'll soon have patient data."

Infectious diseases specialist Dr. Carl Fichtenbaum, Associate Chairman of Medicine for Translational Research and Professor of Clinical Medicine at the University of Cincinnati College of Medicine, commented by email to Reuters Health. "It sounds promising, but very early days and lots more to learn before this becomes the optimal solution."

"We need to understand where the optimal site of protection is in the body," he said. "Is it at the surface where the infection first starts? Is it in the immune system network, like lymph nodes? Do we need a combination of both?"

"It's interesting," he said, "but we need a lot more research to know if this produces higher levels of protection for infections like SARS-CoV-2, and we will need human studies to see if what is proven in animals studies works in humans."

The study was funded by Elicio Therapeutics and all all authors are employees of the company.

SOURCE: Science Advances, online February 5, 2021.