Combining intramuscular and intranasal homologous prime-boost with a chimpanzee adenovirus-based COVID-19 vaccine elicits potent humoral and cellular immune responses in mice

Abstract

The efficacy of many coronavirus disease 2019 (COVID-19) vaccines has been shown to decrease to varying extents against new severe acute respiratory syndrome coronavirus 2 variants, which are responsible for the continuing COVID-19 pandemic. Combining intramuscular and intranasal vaccination routes is a promising approach for achieving more potent immune responses. We evaluated the immunogenicity of prime-boost protocols with a chimpanzee adenovirus serotype 68 vector-based vaccine, ChAdTS-S, administered via both intranasal and intramuscular routes in BALB/c mice. Intramuscular priming followed by an intranasal booster elicited the highest levels of IgG, IgA, and pseudovirus neutralizing antibody titres among all the protocols tested at day 42 after prime immunization compared with the intranasal priming/intramuscular booster and prime-boost protocols using only one route. In addition, intramuscular priming followed by an intranasal booster induced high T-cell responses, measured using the IFN-γ ELISpot assay, that were similar to those observed upon intramuscular vaccination. All ChAdTS-S vaccination groups induced Th1-skewing of the T-cell response according to intracellular cytokine staining and Meso Scale Discovery cytokine profiling assays on day 56 after priming. This study provides reference data for assessing vaccination schemes of adenovirus-based COVID-19 vaccines with high immune efficacy.

Heterologous prime-boost immunisation with mRNA- and AdC68-based 2019-nCoV variant vaccines induces broad-spectrum immune responses in mice

“…However, the proportions of memory B cells and neutralising antibodies were Meanwhile, all vaccination groups induced a Th1-biased cellular immune response, with higher concentrations of Th1-secreted TNF-a, IL-2 and IFN-g in the five intramuscular-only vaccination groups than those in the intranasal vaccination and homologous prime-boost groups. These findings were consistent with our previous results (44).…”

An Adenovirus-Based Recombinant Herpes Simplex Virus 2 (HSV-2) Therapeutic Vaccine Is Highly Protective against Acute and Recurrent HSV-2 Disease in a Guinea Pig Model

“…T-cell response plays an important protective role against HSV-2 infection [ 25 ]. Here, all adenovirus vaccination groups induced Th1 type T-cell response after two immunizations, similar to recent studies [ 47 , 48 ]. The combination-expressed group (rAd-gD2 + rAd-ΔUL25) induced a significantly higher level of the Th1-type immune response, indicating the enhancing effect of rAd-ΔUL25 in inducing a cellular immune response.…”

SARS-CoV-2 S1 Subunit Booster Vaccination Elicits Robust Humoral Immune Responses in Aged Mice

“…Two limitations of this study were T-cell immunity and SARS-CoV-2 challenge, which were not performed to test the cellular immunity and to assess the protection efficiency of booster vaccination. However, various studies have reported previously that T-cell immunity was activated after a booster [23, 35, 46, 47]. Homologous and heterologous boosters in health care workers who had received a priming dose of Ad26.COV2.S Covid-19 vaccine resulted in higher levels of T-cell responses than non-booster group, although T-cell response was significantly larger with mRNA-based vaccines (91%) than with the homologous booster (72%) [23].…”