Intranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice

Abstract

We have developed a COVID-19 vaccine, hAd5 S-Fusion + N-ETSD, that expresses SARS-CoV-2 spike (S) and nucleocapsid (N) proteins with modifications to increase immune responses delivered using a human adenovirus serotype 5 (hAd5) platform. Here, we demonstrate subcutaneous (SC) prime and SC boost vaccination of CD-1 mice with this dual-antigen vaccine elicits T-helper cell 1 (Th1) biased T-cell and humoral responses to both S and N that are greater than those seen with hAd5 S wild type delivering only unmodified S. We then compared SC to intranasal (IN) prime vaccination with SC or IN boosts and show that an IN prime with an IN boost is as effective at generating Th1 biased humoral responses as the other combinations tested, but an SC prime with an IN or SC boost elicits greater T cell responses. Finally, we used a combined SC plus IN (SC + IN) prime with or without a boost and found the SC + IN prime alone to be as effective in generating humoral and T-cell responses as the SC + IN prime with a boost. The finding that SC + IN prime-only delivery has the potential to provide broad immunity—including mucosal immunity—against SARS-CoV-2 supports further testing of this vaccine and delivery approach in animal models of viral challenge.

Induction of Th1 and Th2 in the protection against SARS-CoV-2 through mucosal delivery of an adenovirus vaccine expressing an engineered spike protein

“…Recently, a study showed that express wild-type or modified S protein by Ad5 via neither s.c. nor i.n. immunization was able to detect the IL-4 + T cell response [46] . However, our studies showed that AdCoV2s elicited strong antibody response (e.g., AdCoV2-S; Fig.…”

Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates

“…COH04S1 and MVA-SARS-2-S, an MVA vector expressing S alone, are currently the only MVA-based SARS-CoV-2 vaccines that are clinically evaluated 61 . In addition, COH04S1 and a recently developed adenovirus vector approach are currently the only clinically evaluated SARS-CoV-2 vaccines that utilize an antigen combination composed of S and N 62 . These findings highlight the potential importance of COH04S1 as a second generation multiantigenic SARS-CoV-2 vaccine to contribute to the establishment of longterm protective immunity to prevent COVID-19 disease.…”

Intranasal COVID-19 vaccines: From bench to bed

“… Type Vaccine Target Route (no. of doses) Animal used Ad-vectored vaccine ChAd-SARS-CoV-2-S S protein IN (1) hACE2 mice 33 , 43 and rhesus macaques 42 ChAd-SARS-CoV-2-S S protein IM or IN, (1) Golden Syrian hamsters 35 AdCOVID RBD protein IN (1) Mice 44 Ad5.SARS-CoV2-S1 S1 protein IN or SC, (1) Mice 45 ChAdOx1 S protein IM or IN, (1 or 2) Ferrets 47 , hamsters and rhesus macaques 46 Ad5-nCoV Full-length S protein IM or IN, (1); or oral + IN, simultaneously, (1) Mice and ferrets 38 Ad5-S-nb2 S protein IM or IN, (1) Mice and rhesus macaques 39 Ad5‐N N protein IN (2) Mice 52 AdC7-S, AdC7-RBD and AdC7-RBD-tr2 S, RBD or tandem-repeat dimeric RBD IM or IN, (2) hACE2 mice 50 – S and N proteins SC or IN, (1) Mice 51 Lentivirus-vectored vaccine – S protein IP + IN (2); or IM + IN (2) Mice and golden hamsters 57 – S protein IM + IN, (2) hACE2 mice 58 Influenza virus-vectored vaccine ∆NA(RBD)-Flu virus RBD pro...…”

“… 50 N protein alone, or combined with S protein, can also be the target of Ad vector-based IN vaccines, which could induce strong N- and S-specific immune responses in mice. 51 , 52 Further studies are necessary to strengthen the potential of N protein as an ideal vaccine target for SARS-CoV-2.…”