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. 2022 Nov:148:52-64.
doi: 10.1016/j.rvsc.2022.05.003. Epub 2022 May 29.

A subunit vaccine candidate based on the Spike protein of SARS-CoV-2 prevents infectious virus shedding in cats

Sandra Barroso-Arévalo  1 , Lidia Sánchez-Morales  2 , Mercedes Domínguez  3 , Teresa García-Seco  4 , María A Risalde  5 , Ignacio García-Bocanegra  6 , Lucas Domínguez  2 , José M Sánchez-Vizcaíno  2
Affiliations

A subunit vaccine candidate based on the Spike protein of SARS-CoV-2 prevents infectious virus shedding in cats

Sandra Barroso-Arévalo et al. Res Vet Sci. 2022 Nov.

Abstract

Of the numerous animal species affected by the SARS-CoV-2 virus, cats are one of the most susceptible, and cat-to-cat transmission has been described. Although cat-to-human infection has not, as yet, been demonstrated, preventive measures should be taken in order to avoid both viral infection in cats and transmission among them. In this respect, the application of an effective vaccine to at-risk populations would be a useful tool for controlling the disease in this species. Here, we test a new vaccine prototype based on the Spike protein of the virus in order to prevent infection and infectious virus shedding in cats. The vaccine employed in experimentation, and which is easily produced, triggered a strong neutralizing antibody response in vaccinated animals. In contrast to that which occurred with control animals, no infectious virus was detected in the oropharyngeal or rectal swabs of vaccinated cats submitted to a SARS-CoV-2 challenge. These results are of great interest as regards future considerations related to implementing vaccination programs in pets. The value of cats as vaccination trial models is also described herein.

Keywords: Cats; SARS-CoV-2; Spike protein; Subunit vaccine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Outline of the procedure carried out during the experiment on animals VAC1, VAC2, CINF1, and CINF2.
Fig. 2
Fig. 2
Average value of Ct in oropharyngeal swabs of animals VAC1 (euthanized on 16 DPI), VAC2 (euthanized on 21 DPI), CINF1 (euthanized on 21 DPI), and CINF2 (euthanized on 16 DPI), from 1 DPI to 21 DPI. Ct of 40 corresponds to a negative result of RT-qPCR.
Fig. 3
Fig. 3
Percentage of inhibition in VAC1 and VAC2 from 20 DPV (day post-vaccination; one day before the second dose of the vaccine), and CINF1 and CINF2 from 1 DPI (day post-infection). The discontinued line indicates the day of infection.
Fig. 4
Fig. 4
Interleukin 6 (IL-6) levels in serum in vaccinated cats (VAC1 and VAC2) and control infection cats (CINF1 and CINF2) based on the sampling time (DPI: day post-infection).
Fig. 5
Fig. 5
Interferon-gamma (IFN- γ) levels in serum in vaccinated cats (VAC1 and VAC2) and control infection cats (CINF1 and CINF2) based on the sampling time (DPI: day post-infection).
Fig. 6
Fig. 6
Viral loads based on Ct values in tissues from animal VAC2 euthanized on 21 DPI. Only tissues positive to two or three targets (Sarbeco, IP2, and IP4) are represented.
Fig. 7
Fig. 7
Viral loads based on Ct values in tissues from animal CINF1 euthanized on 16 DPI. Only tissues positive to two or three targets (Sarbeco, IP2, and IP4) are represented.
Fig. 8
Fig. 8
Viral loads based on Ct values in tissues from animal CINF2 euthanized on 21 DPI. Only tissues positive to two or three targets (Sarbeco, IP2, and IP4) are represented.
Fig. 9
Fig. 9
Pulmonary lesions found in vaccinated and non-vaccinated cats after SARS-CoV-2 infection. The lungs of VAC2 and CINF2 had intense alveolar congestion and edema (black asterisk) (A and C, respectively), while, the presence of these lesions was moderate in VAC1 and CINF1 (B and D, respectively). E) Lung of VAC1, with mild alveolar edema (black asterisks), small areas of atelectasis (green asterisk), and focal alveolar macrophages hyperplasia (inset). F) Lung of VAC2, with moderate alveolar edema with some collapsed alveoli (black asterisks) and small atelectasis areas (green asterisk), along with the presence of microthrombi in small and medium vascular vessels (grey arrow), associated with a great number of platelets positive to the anti-Factor-VIII antibody when tested using immunohistochemistry (inset). G) Lung of CINF1, with severe alveolar edema and proteinaceous exudates (black asterisks), perivascular edema (black arrowhead) and a slight thickening of the alveolar septa owing to mononuclear cell infiltrations and deposits of fibrin positive to Fraser Lendrum technique (inset, pink). H) Lung of VAC2, with moderate alveolar edema (black asterisks) and small atelectasis areas (green asterisks), perivascular edema (black arrowhead) and thrombi (grey arrow) in medium vascular vessels, along with thickening of the alveolar septa owing to mononuclear cell infiltrations and deposits of fibrin positive to Fraser Lendrum technique (inset, pink). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 10
Fig. 10
Pulmonary histopathological findings and their corresponding semi-quantitative grades of evaluation in VAC1, VAC2, CINF1, and CINF2 cats infected with SARS-CoV-2.
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