A Self-Biomineralized Novel Adenovirus Vectored COVID-19 Vaccine for Boosting Immunization of Mice

Abstract

SARS-CoV-2 has caused more than 3.8 million deaths worldwide, and several types of COVID-19 vaccines are urgently approved for use, including adenovirus vectored vaccines. However, the thermal instability and pre-existing immunity have limited its wide applications. To circumvent these obstacles, we constructed a self-biomineralized adenovirus vectored COVID-19 vaccine (Sad23L-nCoV-S-CaP) by generating a calcium phosphate mineral exterior (CaP) based on Sad23L vector carrying the full-length gene of SARS-CoV-2 spike protein (S) under physiological condition. This Sad23L-nCoV-S-CaP vaccine was examined for its characteristics of structure, thermostability, immunogenicity and avoiding the problem of preexisting immunity. In thermostability test, Sad23L-nCoV-S-CaP could be stored at 4 °C for over 45 days, 26 °C for more than 8 days and 37 °C for approximately 2 days. Furthermore, Sad23L-nCoV-S-CaP induced higher level of S-specific antibody and T cell responses, and was not affected by the pre-existing anti-Sad23L immunity, suggesting it could be used as boosting immunization on Sad23L-nCoV-S priming vaccination. The boosting with Sad23L-nCoV-S-CaP vaccine induced high titers of 10 5.01 anti-S1, 10 4.77 anti-S2 binding antibody, 10 3.04 pseudovirus neutralizing antibody (IC 50 ), and robust T-cell response of IFN-γ (1466.16 SFCs/10 6 cells) to S peptides, respectively. In summary, the self-biomineralization of the COVID-19 vaccine Sad23L-nCoV-S-CaP improved vaccine efficacy, which could be used in prime-boost regimen for prevention of SARS-CoV-2 infection in humans. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00434-3.

Vaccination of cats with Sad23L-nCoV-S vaccine candidate against major variants of SARS-CoV-2

“…24 Sad23L was already used in the development of Zika and COVID-19 vaccines and was not cross-reactive with human adenovirus serotype 5 (Ad5) vector. 17,18,24 These vaccines were examined by intramuscularly inoculating mice, common marmosets, and rhesus monkeys, inducing the sufficient protection against Zika virus challenging 25 or highly protective immunity to SARS-CoV-2 infection 17,18 and presenting potential vaccine candidates for humans. In this study, cats were vaccinated with two injections of Sad23L-nCoV-S vaccines, acquiring the strongly specific NAb and IFN-g secretion T cell response to SARS-CoV-2.…”

“…The replication-defective adenovirus-vectored Sad23L-nCoV-S vaccine encoding the full-length S protein gene of SARS-CoV-2 (Wuhan-1 isolate; GenBank: MN908947.3) was constructed and produced as described previously. 17,18 Briefly, based on the genome backbone of simian adenovirus serotype 23 (GenBank: AY530877. 1), the Sad23L vector was constructed by deleting the E1 and E3 regions, and the open reading frame 6 (ORF6) within E4 region was replaced by Ad5 element in order to improve the virus propagation efficiency.…”

“…[12][13][14][15][16] Previously, we developed simian adenovirus serotype 23 vector (Sad23L) and human adenovirus serotype 49 vector (Ad49L)-based COVID-19 vaccines (Sad23L-nCoV-S and Ad49L-nCoV-S) and examined their immunogenicity in mice and rhesus monkeys. 17,18 Here, we evaluated the protective immunity of Sad23L-nCoV-S vaccine against wild-type strain and Alpha, Beta, Gamma, Delta, and Omicron variants of pseudotyped SARS-CoV-2 in cats.…”

Fighting Fire with Fire: Immunogenicity of Viral Vectored Vaccines against COVID-19

“…IN delivery induced approximately 6-fold higher antibody titers than IM delivery, in contrast to the ChAdOx1 nCoV-19 vaccine that elicited higher antibodies through the IM route in ferrets [41][42][43]. In BALB/c mice, a prime-boost IM administration of a novel Ad-vectored vaccine (Sad23L-nCoV-S) and its self-biomineralized form (Sad23L-nCoV-S-CaP) elicited potent humoral responses [44]. In cynomolgus macaques, a single IM immunization of 5 × 10 10 vp of a gorilla adenoviralvectored vaccine (GRAd-COV2) encoding a prefusion-stabilized S induced potent IgG and NAb responses [45].…”

Engineering optimal vaccination strategies: effects of physical properties of the delivery system on functions

“…20,55 Similar inorganic materials, such as calcium phosphate, mesoporous silica, and zinc oxide, have the potential for antigen delivery and adjuvant activity in vaccines. [56][57][58][59][60] Calcium phosphate has been used as an adjuvant in the diphtheriatetanus-pertussis (DTP)-polio vaccines. 61 Other inorganic materials are still at the research stage and have not been used in a clinical setting.…”