Could an intranasal adjuvant to vaccines boost immunity against SARS-CoV-2 variants?

While the approved vaccines aimed at neutralizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have proven effective in decreasing the risk of severe infection and mortality, it may take months for the whole world to be effectively neutralized. Another ongoing issue is the increasing emergence of new variants that may compromise the vaccine’s effectiveness by evading the immune system.

A research team from the University of Michigan Medical School, USA, developed a supplementary intranasal treatment to improve COVID-19 vaccine response and its effects on long-lasting immunity from other variants, such as the B.1.351 variant first found in South Africa.

“Together, our data demonstrate that combination of NE/IVT DI offers a promising strategy for promoting both robust antibody and T cell responses to improve protection against SARS-CoV-2,” wrote the researchers.

Importantly the robust neutralizing antibody response induced by NE/IVT DI provides sterilizing cross-protective immunity which will likely be further strengthened in the context of the strong T cell responses induced. Thus, this adjuvant has the potential to also improve the breadth of induced immunity against future drift variants.”

The study “A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine” is available as a preprint on the bioRxiv* server, while the article undergoes peer review.

Developing safe a safe adjuvant treatment

The research team used recombinantly produced S1 subunit of the SARS-CoV-2 spike protein to create a combination intranasal adjuvant with a nanoemulsion-based adjuvant that would then activate toll-like receptors and protein-coding gene NLRP3 with the RNA agonist RIG-I.

The team previously mentioned an acceptable safety profile in the adjuvant treatment based on the results of a phase I trial and another ongoing phase I trial. They analyzed the acute cytokine response from several cytokine levels in a SARS-CoV-2 RBD model antigen in mice to confirm this further. They found that mice given the adjuvant treatment showed little to no acute inflammatory cytokine activity, with only IL-6 levels slightly elevated.

Adjuvant treatment boosted vaccine response

The researchers then looked at the adjuvant treatment’s effect on the humoral response.

Previous studies evaluating vaccine candidates for related SARS-CoV have demonstrated that the S1 subunit induces a comparable humoral immune response as the full-length S protein while avoiding the problems of vaccine-associated enhanced respiratory disease and antibody-dependent enhancement induced by some of the vaccine formulations tested with the native full-length S protein.”

The team found a lack of immune response when 6- to 8-week-old mice were vaccinated with the S1 subunit of SARS-CoV-2 in the absence of adjuvant treatment. However, when another group was given the adjuvant treatment as a booster, the team found S1-specific antibody levels, which the authors suggest “improved synergistic effects in early antibody titers with the combined adjuvant upon further optimization of antigen dose.” The antibody levels were further elevated after the second and then third immunization compared to the antibody levels in mice exposed to the S1 subunit only.

Long-lasting immunity observed with different COVID strains

With the growing rise of COVID-19 variants worldwide, the team also looked at how effective the adjuvant treatment is in neutralizing the S protein's mutations. They found mice exposed to a Wuhan-Hu-1 isolate of SARS-CoV-2 displayed little to no antibody levels in their blood plasma. However, mice given adjuvant treatment as a first boost immunization after the sixth week showed antibody levels. With a second boost administered on the tenth week, the antibody levels increased by two magnitudes suggesting the adjuvant was potentially useful in promoting antibodies.

The researchers then used a different strain called MA-SARS-CoV-2 that contained the N501Y and H655Y gene mutation and continued to find neutralizing antibody levels in immunized mice after two immunizations of adjuvant treatment.

Thus, this further suggests that the combined adjuvant may strengthen the quality of the antibody response, providing a protective advantage against divergent variants,” wrote the researchers.

Based on the high neutralization observed after three immunizations with the adjuvant treatment, the authors suggest sterilizing immunity is achievable against a heterologous variant containing the N501 mutations currently found in the B.1.1.7 and B.1.351 variant.

The adjuvant treatment also displayed more robust cellular immunity by enhancing the TH1-biased cellular response and increased IL-2, IP-10, and TNF-α in the spleen and draining lymph nodes.

The authors conclude the results show strong evidence of the adjuvant therapy increasing immunity by increasing antibody levels and inducing a cytokine environment favoring type 1 immune responses and T cell response.

*Important Notice

bioRxiv 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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