Intranasal vaccination of hamsters with a Newcastle disease virus vector expressing the S1 subunit protects animals against SARS-CoV-2 disease

Abstract

The coronavirus disease-19 (COVID-19) pandemic has already claimed millions of lives and remains one of the major catastrophes in the recorded history. While mitigation and control strategies provide short term solutions, vaccines play critical roles in long term control of the disease. Recent emergence of potentially vaccine-resistant and novel variants necessitated testing and deployment of novel technologies that are safe, effective, stable, easy to administer, and inexpensive to produce. Here we developed three recombinant Newcastle disease virus (rNDV) vectored vaccines and assessed their immunogenicity, safety, and protective efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice and hamsters. Intranasal administration of rNDV-based vaccine candidates elicited high levels of neutralizing antibodies. Importantly, the nasally administrated vaccine prevented lung damage, and significantly reduced viral load in the respiratory tract of vaccinated animal which was compounded by profound humoral immune responses. Taken together, the presented NDV-based vaccine candidates fully protected animals against SARS-CoV-2 challenge and warrants evaluation in a Phase I human clinical trial as a promising tool in the fight against COVID-19.

Characterization of Systemic and Mucosal Humoral Immune Responses to an Adjuvanted Intranasal SARS-CoV-2 Protein Subunit Vaccine Candidate in Mice

“…The spike protein of SARS-CoV-2 is the primary antigenic target of currently approved vaccines due to its high immunogenicity, abundant viral surface expression and ability to elicit both humoral and cell-mediated responses [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. The spike protein also demonstrates effective mucosal and systemic induction of humoral and cell-mediated immunity through oral and intranasal vaccination in various animal models [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Notably, a majority of these vaccine candidates are based on an adenoviral platform which expresses the spike trimer protein of the parental strain of SARS-CoV-2.…”

Development of Nasal Vaccines and the Associated Challenges

“…In clinical trials, viral vector-based vaccines may prove to be significantly ineffective when the same vector or similar vectors are used, as the efficacy of human vaccines is reduced in individuals that have been previously infected with these viruses. Several non-homologous viral vectors have been studied extensively, among which is the Newcastle disease virus (NDV), which was used as a vaccine vector for SARS in 2003 and SARS-CoV-2 in 2019 [ 165 , 166 , 167 ]. NDV vectors expressing wild-type S or membrane-anchored S and without polybasic cleavage sites may also be used as vaccine vectors against SARS-CoV-2.…”