Intradermal Immunization of SARS-CoV-2 Original Strain Trimeric Spike Protein Associated to CpG and AddaS03 Adjuvants, but Not MPL, Provide Strong Humoral and Cellular Response in Mice

Abstract

Despite the intramuscular route being the most used vaccination strategy against SARS-CoV-2, the intradermal route has been studied around the globe as a strong candidate for immunization against SARS-CoV-2. Adjuvants have shown to be essential vaccine components that are capable of driving robust immune responses and increasing the vaccination efficacy. In this work, our group aimed to develop a vaccination strategy for SARS-CoV-2 using a trimeric spike protein, by testing the best route with formulations containing the adjuvants AddaS03, CpG, MPL, Alum, or a combination of two of them. Our results showed that formulations that were made with AddaS03 or CpG alone or AddaS03 combined with CpG were able to induce high levels of IgG, IgG1, and IgG2a; high titers of neutralizing antibodies against SARS-CoV-2 original strain; and also induced high hypersensitivity during the challenge with Spike protein and a high level of IFN-γ producing CD4+ T-cells in mice. Altogether, those data indicate that AddaS03, CpG, or both combined may be used as adjuvants in vaccines for COVID-19.

Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection

“…Regarding survival and body weight lost, nonvaccinated animals succumbed to infection, while vaccination by both routes prevented viral spread into distal areas of the brain and protected all infected animals. These results are in line with other studies showing the effectiveness of different vaccine formulations administered by different routes [36] and indicate that our vaccine candidate is effective irrespective of the administration route. However, major differences between s.c. and i.n.…”

Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants

“…This could lead to heterogeneity in the response within mice groups, with a similar profile as it has been observed in previous studies using DNA vaccination ( 26 ). On the other hand, several published works have also shown that intradermal immunization can lead to strong immune activation following vaccination with different technologies in mice and humans and using low vaccine doses ( 59 – 63 ).…”

Al-fumarate, a Metal-Organic Framework encapsulating antigen as a potent, versatile and resorbable vaccine adjuvant

“…A myriad of alternative adjuvants has been developed either with different chemical compositions (e.g. Freund's adjuvant, squalene, liposomes, MF59, lipids, cell exosomes or bacteria wall, etc), [18][19][20][21][22][23][24][25][26][27] or structurally different Al-based adjuvants, 15,28 but only a few have reached approval for human use as many exhibit either unacceptable side effects, insufficient immune responses, stability issues or difficulties in scaling-up. [29][30][31][32] Alternatively, the lack of cellular response in traditional Al-adjuvants can be compensated by the addition of immune orienteers (oligonucleotides, 33 imidazoquinoline, 34 TLR7 agonists 35 ).…”