Abstract
SARS-CoV-2 is a viral respiratory pathogen responsible for the current global pandemic and the disease that causes COVID-19. All current WHO approved COVID-19 vaccines are administered through the muscular route. We have developed a prototype two-dose vaccine (BReC-CoV-2) by combining the Receptor Binding Domain (RBD) antigen, via conjugation to Diphtheria toxoid (EcoCRM®). The vaccine is adjuvanted with Bacterial Enzymatic Combinatorial Chemistry (BECC), BECC470. Intranasal (IN) administration of BreC-CoV-2 in K18-hACE2 mice induced a strong systemic and localized immune response in the respiratory tissues which provided protection against the Washington strain of SARS-CoV-2. Protection provided after IN administration of BReC-CoV-2 was associated with decreased viral RNA copies in the lung, robust RBD IgA titers in the lung and nasal wash, and induction of broadly neutralizing antibodies in the serum. We also observed that BReC-CoV-2 vaccination administered using an intramuscular (IM) prime and IN boost protected mice from a lethal challenge dose of the Delta variant of SARS-CoV-2. IN administration of BReC-CoV-2 provided better protection than IM only administration to mice against lethal challenge dose of SARS-CoV-2. These data suggest that the IN route of vaccination induces localized immune responses that can better protect against SARS-CoV-2 than the IM route in the upper respiratory tract.
Highlights
As of January 2020, when the first SARS-CoV-2 genome was released, tremendous progress has been made in developing vaccines against COVID-19
Intramuscular administration of Receptor Binding Domain (RBD) or RBD-EcoCRM® adjuvated with BECC438 resulted in similar RBD IgG titers at 2 weeks post boost; when administered intranasally, RBD-EcoCRM® with BECC438 elicited greater RBD IgG titers compared to RBD (Fig. 1)
RBD-EcoCRM® adjuvanted with BECC470 elicits robust antibody responses in CD1 mice In this study, we focused on further investigating RBD-EcoCRM® and BECC470 (BReC-CoV-2)
Summary
As of January 2020, when the first SARS-CoV-2 genome was released, tremendous progress has been made in developing vaccines against COVID-19. There are greater than 200 vaccines being developed worldwide to combat SARS-CoV-2, the causative agent of the COVID-19 pandemic[1]. Approved vaccinations for COVID-19 and most vaccines in development have been administered or designed to be given through the intramuscular route. Each route of vaccination provides a unique protection profile for respiratory viruses. Intramuscular vaccination produces a predominantly systemic immune response dominated mostly by serum IgG and, resulting in minimal to no detectable mucosal immune response at the site of infection[3,4]. The vaccine response generated after intramuscular immunization can leave the upper respiratory tract vulnerable to viral replication and dissemination because it lacks the mucosal immune response generated by natural infection or intranasal vaccination[3]. Intranasal vaccination may provide both a systemic and a robust local IgA response, as what occurs during natural infection, which may lead to total protection[3]. In pre-clinical studies, non-human primates vaccinated intramuscularly with Pfizer-BioNtech (BNT162b2) intramuscularly and challenged with SARS-CoV-2 had detectable
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