Oral Vaccination Protects Against Severe Acute Respiratory Syndrome Coronavirus 2 in a Syrian Hamster Challenge Model

Abstract

Background: Vaccines that are shelf stable and easy to administer are crucial to improve vaccine access and reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission around the world.

Methods: In this study, we demonstrate that an oral, adenovirus-based vaccine candidate protects against SARS-CoV-2 in a Syrian hamster challenge model.

Results: Hamsters administered 2 doses of VXA-CoV2-1 showed a reduction in weight loss and lung pathology and had completely eliminated infectious virus 5 days postchallenge. Oral immunization induced antispike immunoglobulin G, and neutralizing antibodies were induced upon oral immunization with the sera, demonstrating neutralizing activity.

Conclusions: Overall, these data demonstrate the ability of oral vaccine candidate VXA-CoV2-1 to provide protection against SARS-CoV-2 disease.

Keywords: COVID; SARS-CoV-2; hamster; mucosal; oral vaccine.

Figure 1.

Schematic of Syrian hamster challenge study. Hamsters were immunized on weeks 0 and 4 (or just week 0 for 1 dose groups) and challenged intranasally (i.n.) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on week 8. VXA-COV2-1 was given at 1e9 IU per hamster (either orally or by i.n.). As a control, 5 µg of SARS-CoV protein was given to each animal in the protein group. Untreated animals were given no vaccine, but they were challenged at the same time as the vaccine groups. Serum was taken at day 0, 4 weeks, 8 weeks, and day 5 postchallenge. Lung tissue was taken at day 5 postchallenge. N = 8 per group. Created with BioRender.com.

Figure 2.

Vaccinated hamsters are protected from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated weight loss and lung pathology. (A) Animals were monitored for weight for 5 days after challenge. Means (±standard error of the means [SEMs]) are shown for each group. (B) Lung weights on day 5 were taken and normalized by the actual animal weight to calculate a percentage of body weight. Means (±SEMs) are shown for each group, one-way analysis of variance statistical analysis was performed among the groups, with all groups compared with the no vaccine group. (C) Histology scores of lungs. (D) Histopathology of the lungs. Lung lobes were collected, trimmed, and processed routinely, paraffin embedded, sectioned at 4 µm, and stained with hematoxylin and eosin for microscopic examination.

Figure 3.

Two-dose oral or intranasal vaccination generates high titer antibodies that are neutralizing. (A) S-specific immunoglobulin G in the serum at day 0, 28, and 54 postvaccination and 5 days postchallenge was measured by enzyme-linked immunosorbent assay (ELISA) and graphed over time. All vaccinated groups generated antibodies. (B) The ability for the antibodies in serum taken at week 8 to neutralize virus was measured in a surrogate viral neutralizing assay (SVNT). Antibodies in the oral and intranasal groups were able to block the binding of ACE-2 to S1 in the competitive ELISA SVNT. One-way analysis of variance statistical analysis was performed among the groups with all groups compared with the no vaccine group.

Figure 4.

Oral and intranasal vaccination decreases virus in the lungs. (A) Lung severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titers as measured by quantitative reverse-transcription polymerase chain reaction (PCR) on day 5 postchallenge. Lung tissues were homogenized, and RNA was extracted and run on a quantitative PCR to detect SARS-CoV-2. Viral titers are substantially reduced in the 2-dose oral and intranasal groups. (B) The 50%tissue culture infective dose (TCID-50) per gram/lung tissue. The lung tissue extract was added to Vero cells in serial dilutions, and wells with cytopathic effect were counted as a measure of infectious dose. One-way analysis of variance statistical analysis was performed among the groups with all groups compared with the no vaccine group.