Abstract
Background: The live-attenuated yellow fever vaccine YF17D holds great promise as alternative viral vector vaccine platform, showcased by our previously presented potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate YF-S0. Besides protection from SARS-CoV-2, YF-S0 also induced strong yellow fever virus (YFV)-specific immunity, suggestive for full dual activity. A vaccine concomitantly protecting from SARS-CoV-2 and YFV would be of great benefit for those living in YFV-endemic areas with limited access to current SARS-CoV-2 vaccines. However, for broader applicability, pre-existing vector immunity should not impact the potency of such YF17D-vectored vaccines.
Methods: The immunogenicity and efficacy of YF-S0 against YFV and SARS-CoV-2 in the presence of strong pre-existing YFV immunity were evaluated in mouse and hamster challenge models.
Findings: Here, we show that a single dose of YF-S0 is sufficient to induce strong humoral and cellular immunity against YFV as well as SARS-CoV-2 in mice and hamsters; resulting in full protection from vigorous YFV challenge in either model; in mice against lethal intracranial YF17D challenge, and in hamsters against viscerotropic infection and liver disease following challenge with highly pathogenic hamster-adapted YFV-Asibi strain. Importantly, strong pre-existing immunity against the YF17D vector did not interfere with subsequent YF-S0 vaccination in mice or hamsters; nor with protection conferred against SARS-CoV-2 strain B1.1.7 (Alpha variant) infection in hamsters.
Interpretation: Our findings warrant the development of YF-S0 as dual SARS-CoV-2 and YFV vaccine. Contrary to other viral vaccine platforms, use of YF17D does not suffer from pre-existing vector immunity.
Funding: Stated in the acknowledgments.
Keywords: Anti-vector immunity; Dual vaccine; SARS-CoV-2 vaccine; Yellow fever vaccine.
【저자키워드】 SARS-CoV-2 vaccine, Yellow fever vaccine., Dual vaccine, Anti-vector immunity, 【초록키워드】 SARS-CoV-2, Efficacy, Vaccine, coronavirus, vaccination, Immunity, Vaccines, hamsters, Infection, SARS-CoV-2 vaccines, virus, cellular immunity, mice, Fever, vaccine candidate, Alpha variant, yellow fever, hamster, platform, pre-existing immunity, single dose, Liver disease, humoral, Viral vector vaccine, acute respiratory syndrome, applicability, SARS-CoV-2 strain, highly pathogenic, benefit, resulting, subsequent, evaluated, induce, interfere, 【제목키워드】 COVID-19 vaccine, Fever, virus infection, PROTECT,