Rapid antibody response induced by mRNA COVID vaccines in mice

The COVID-19 vaccines are unique not only for their fast development or excellent response in preventing severe COVID-19 infection but also for the novel use of mRNA technology in a vaccine. Though, questions have been raised on how mRNA technology works to boost the immune system.

A new study posted in the bioRxiv* preprint server used mouse models to investigate how mRNA vaccines elicit a rapid antibody response. Their findings show two different mRNA vaccines successfully boost antibody levels — IL-5, IL-6, and MCP-1 —5 days after administration.

“The rapid immune kinetics of mRNA vaccines can be an advantageous property that makes them well suited for rapid control of infectious disease outbreaks,” concluded the researchers.

Study: mRNA Vaccines Induce Rapid Antibody Responses in Mice. Image Credit: Corona Borealis Studio / Shutterstock
Study: mRNA Vaccines Induce Rapid Antibody Responses in Mice. Image Credit: Corona Borealis Studio / Shutterstock

Humoral immune response following vaccination

The team studied antibody levels of C57BL/6 mice who were vaccinated with mRNA vaccines expressing the SARS-CoV-2 spike protein at either 1 µg (low) or 4 µg (high) doses. The vaccines were given through the muscle or through the skin.

Other groups of mice serving as control groups were vaccinated intramuscularly with a DNA vaccine.

Using an ELISA assay, the researchers were able to measure the number of spike-specific binding antibodies present in mice.

After 5 days of immunization, mice that were given the 4 µg dose of the mRNA vaccine showed increased spike-specific binding antibody titers. Though antibody titers were much higher with vaccines given intradermally than intramuscularly.

In contrast, antibody titers were not detectable with the DNA vaccine or the low-dose mRNA vaccine.

After a week since vaccination, mice immunized intramuscularly with a high-dose mRNA vaccine continued to show significantly higher antibody titers compared to mice given the DNA vaccine.

At 2 weeks, all mice administered an mRNA vaccine showed dose-dependent antibody responses. In the DNA vaccine group, antibody titers were detectable but lower than the mRNA vaccine group.

After 3 weeks, antibody titers from the DNA vaccine were similar to those observed in mice given the high-dose mRNA vaccine.

The results suggest mRNA vaccines produce rapid antibody responses that are dose and route-dependent.

Kinetics of binding antibody responses of mice immunized with SARS-CoV-2 Spike mRNA and DNA vaccines. C57BL/6 mice were immunized I.M. or I.D. with spike encoding mRNA vaccine (1µg or 4µg/mouse), DNA vaccine (50µg/mouse) or PBS. Binding antibody titers were assessed via ELISA at 0, 5, 7, 14, 21 and 28 days post immunization. Each dot represents an individual animal, bars depict the median and the dotted line shows limit of detection. Statistical analysis was performed using Mann-Whitney test. (I.M = intramuscular; I.D. = intradermal)
Kinetics of binding antibody responses of mice immunized with SARS-CoV-2 Spike mRNA and DNA vaccines. C57BL/6 mice were immunized I.M. or I.D. with spike encoding mRNA vaccine (1µg or 4µg/mouse), DNA vaccine (50µg/mouse) or PBS. Binding antibody titers were assessed via ELISA at 0, 5, 7, 14, 21 and 28 days post immunization. Each dot represents an individual animal, bars depict the median and the dotted line shows limit of detection. Statistical analysis was performed using Mann-Whitney test. (I.M = intramuscular; I.D. = intradermal)

Rising neutralizing antibody levels after vaccination

Mice given a high-dose mRNA vaccine showed neutralizing antibody titers 5 days after immunization. Mice who received the vaccine through the skin showed the highest neutralizing antibody titers.

After 1 week, mice who were given the mRNA vaccine through the muscle showed significantly higher neutralizing antibody titers than mice with the DNA vaccine. But after 3 weeks, neutralizing antibody levels produced from the DNA vaccine were similar to those produced from the mRNA vaccine.

Innate immune responses from mRNA vs DNA vaccination

Next, the research team explored vaccinations’ effects on cytokine and chemokine expression in both types of vaccines. Specifically, they studied immune responses from mice given either a high-dose mRNA vaccine or a high-dose DNA vaccine administered intramuscularly.

Cytokines that are critical for the development of B cells and antibody production were significantly elevated after mRNA vaccination.

IL-5 — a cytokine involved in B cell differentiation to antibody-secreting plasma cells in mice — was significantly higher in mRNA vaccinated mice than in DNA vaccinated mice as early as 5 hours after immunization.

IL-6 — a cytokine needed for B cell proliferation and isotype switching — showed elevated levels 5 hours after mRNA vaccination compared to DNA vaccination.

Major players for antigen-presenting cell activation and migration, including chemokines MCP-1, MIP-1ɑ, MIP-1β, and IP-10 were boosted 5 to 24 hours after mRNA vaccination.

mRNA vaccines produce faster immune response than other vaccine technology

Could mRNA vaccines work for other viruses beyond SARS-CoV-2? The researchers looked into this question by injecting an mRNA vaccine that had the Clade C 459C HIV-1 envelope gp140. For comparison purposes, they also administered a DNA vaccine, a purified protein vaccine, and a rhesus adenovirus 52 vaccine with the same HIV antigen. All vaccines were given intramuscularly.

Three days since the mRNA vaccination, the research team detected low antibody titers. But after 5 days, robust antibody responses were observed.

During this timeframe, all other non-mRNA vaccines did not elicit antibody responses.

At 3 weeks since immunization, all four vaccines showed similar and robust antibody titers.

The results indicate mRNA vaccines produce a more rapid immune response than other vaccine technologies. Additionally, mRNA vaccines have the potential for use in other infectious diseases.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Jocelyn Solis-Moreira

Written by

Jocelyn Solis-Moreira

Jocelyn Solis-Moreira graduated with a Bachelor's in Integrative Neuroscience, where she then pursued graduate research looking at the long-term effects of adolescent binge drinking on the brain's neurochemistry in adulthood.

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