The new recombinant, adjuvanted vaccine against herpes zoster has a very different mechanism of action compared to most other vaccines, according to a new study, and might be a model for more effective immunization in older people.

While most vaccines are manufactured using a weakened form of a virus, Shingrix is made from just a single protein—known as glycoprotein E—that comes from the outer shell of the herpes zoster virus. The vaccine also contains an adjuvant to increase effectiveness.

As a result, according to a study published in the Journal of Infectious Diseases, that herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, “was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials” involving patients older than age 50 and 70 years, respectively.

So effective, in fact, that the Westmead Institute for Medical Research–led study authors suggest the model is an important step in vaccine development, noting, “The ability of this vaccine to induce such persistent antibody and polyfunctional CD4 T-cell responses in older adults are likely important mechanisms by which HZ/su drives the high efficacy against HZ. HZ/su demonstrates that the use of AS01B in the vaccine can overcome immunosenescence. We therefore consider HZ/su to be an important step in the design of future vaccines in this age group. Further studies will be needed to determine the precise underlying mechanisms.”

For the two current studies, participants received two doses of HZ/su or placebo, 2 months apart. Results indicate that, after vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. The study reports that geometric mean anti-gE antibody concentrations increased 39.1-fold over baseline in HZ/su recipients at 1 month and 8.3-fold over baseline after 36 months.

In addition, a gE-specific CD42+ T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients, while median CD42+ T-cell frequencies increased 24.6-fold at 1 month and 7.9-fold at 36 months over baseline in HZ/su recipients. Those levels remained 5.6-fold or more above baseline in all age groups at 36 months, according to the researchers, who add that the proportion of CD4 T cells expressing all four activation markers increased over time in all age groups.

“Our research shows that the vaccine stimulates your immune system to produce more antibodies and it generates a 24-fold increase in T cells. This is 12 times higher than other less effective shingles vaccines,” said lead author Anthony L. Cunningham, MD, MBBS, explaining, “When people reach their 50s and 60s, T cell immunity declines allowing shingles to strike. That’s why our adult vaccine is directed specifically at T cell immunity.”

The study concludes, “Most HZ/su recipients developed robust immune responses persisting for three years following vaccination.”

"This is quite remarkable because there are no other vaccines that perform nearly so well for people in their 70s and their 80s. We are seeing results comparable to those of childhood vaccinations,” Cunningham added. "We anticipate that this protection will actually last much, much longer. We are now measuring the efficacy of the vaccine over the next 10 years and are very optimistic about the results.”