Low-dose Moderna COVID-19 vaccine generates long-lasting immune response

A new study from scientists at the La Jolla Institute of Immunology (LJI) answers the question: how long does immunity against COVID-19 last in vaccinated people?

As they report in Science, a low dose of Moderna vaccine lasts for at least six months and there is no indication that those vaccinated will need a booster.

“This time is critical because that is when true immune memory is formed,” said LJI assistant research professor Daniela Weiskopf, Ph.D., who co-led the study with the professors. LJI Alessandro Sette, Dr. Biol Sci., And Shane Crotty, Ph.D.

In fact, while the Moderna COVID-19 vaccine (mRNA-1273) led to strong responses in CD4 + T cells (helper), CD8 + T cells (killer), and antibodies for at least six months after participants in the clinical trial were fully vaccinated, it is likely that the immune response could last much longer. The researchers also show that this strong immune memory lasted across all age groups tested, including people over 70, a demographic group particularly vulnerable to severe COVID-19.

“The immune memory was stable, and it was impressive,” Crotty adds. “It is a good indicator of the durability of mRNA vaccines.”

Comparison of Moderna vaccine to natural immunity

Researchers compared recovered COVID-19 patients to vaccine trial participants who received a 25 microgram dose of Moderna vaccine during Phase 1 clinical trials (supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health).

“We wanted to see if a quarter of the dose is able to induce an immune response,” says study lead author Jose Mateus Triviño, Ph.D., postdoctoral fellow at LJI. “We had the opportunity to receive samples from the original Moderna / NIH Phase 1 trial participants who received two 25 microgram injections of the vaccine, 28 days apart.”

This vaccine dose is a quarter of the 100 microgram dose of Moderna urgently authorized by the Food and Drug Administration (FDA). Although researchers are unsure whether this lower dose is as effective as the standard dose, this new study shows that the response of T cells and antibodies in the lower dose group is still strong.

In fact, researchers found that the Moderna vaccine stimulates an adaptive immune response to the SARS-CoV-2 spike protein (a key target) almost identical to the immune system’s response to a natural infection with SARS-CoV- 2. “The answer is comparable,” Weiskopf explains. “It’s not higher and it’s not lower.”

The new study does not show that a lower dose of Moderna vaccine offers the same protection as the standard dose. “It would take a clinical trial to tell you how protective the lower dose is,” says Crotty.

Cold viruses prepare the immune system

The new research also shows the power of “cross-reacting” T cells. In a 2020 Science study, the LJI team showed that T cells in people who had recovered from cold coronaviruses could respond to the new coronavirus, SARS-CoV-2. At the time, they weren’t sure if this cross-reactivity could actually protect against COVID-19.

“Understanding the role of cross-reacting T cells is important because T cells play an important role in controlling and resolving COVID-19 infections,” says Sette.

For the new study, the researchers found that people with cross-reacting T cells had significantly stronger CD4 + T cell and antibody responses to both doses of the vaccine.

“If you have this immune reactivity, your immune system can react more quickly against the virus,” says Sette. “And several studies have shown that how quickly the immune system responds is key.”

Moderna vaccine activates ‘killer’ T cells

The team also filled a significant gap in research into the COVID-19 vaccine. So far, many studies have shown an effective CD4 + T cell response to Moderna vaccine, but data on CD8 + T cells were lacking.

“We know that naturally infected and cured people develop excellent CD8 + T cell responses against SARS-CoV-2; however, the generation of CD8 + T cells by mRNA vaccines was of concern,” said Mateus Triviño.

The new study shows a strong CD8 + T cell response to the low-dose Moderna vaccine, similar to the response after a patient battles a natural infection with SARS-CoV-2, says Sette, a renowned T cell expert.

“We are seeing a strong response from CD8 + T cells; and we have shown it using several tests, ”adds Weiskopf.

Future :

Will this same vaccine sustainability hold true for other types of COVID-19 vaccines? Weiskopf and his colleagues are investigating. Meanwhile, Weiskopf says real-world data suggests immune memory lasts.

“The people in hospitals are the ones who are not vaccinated,” she says.

The researchers are also interested in how the durability of the Moderna vaccine compares to other COVID-19 vaccines in use.