Study evaluates efficacy of candidate SARS-CoV-2 subunit vaccine to protect endangered black-footed ferrets

In a recently published study Viruses, Researchers evaluated the safety, efficacy, and immunogenicity of a candidate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine in black-footed ferrets (BFF). They examined the susceptibility of endangered North American mammals to the virus.

Study: Immunogenicity, Safety, and Antiviral Efficacy of a SARS-CoV-2 Vaccine Candidate Subunit in Captive Black-footed Ferrets (Mustela nigripes) and Susceptibility to Viral Challenge. Photo credit: Piskova Photo/Shutterstock

Background

Mustela nigripes, or black-footed ferrets, are endangered North American mammals in the Mustelidae family. Diseases wiped out all but a few of the last remaining BFF population. Surviving BFFs have been bred in captivity at several facilities in North America to restore breeding populations and improve their survival in the wild.

Recently, the 2019 coronavirus disease (COVID-19) pandemic revealed that house ferrets and related minks, like some other captive animals in zoos, are susceptible to SARS-CoV-2.

Given the susceptibility of closely related species to SARS-CoV-2, additional measures such as physical distancing, ultraviolet air filtration, and personal protective equipment (PPE) have been implemented in BFF breeding facilities to prevent exposure to the virus. However, such measures are expensive and unsustainable over the long term, hampering the breeding program.

Development of SARS-CoV-2 vaccines for BFFs could effectively protect existing populations from COVID-19 and limit transmission of the virus between animals and their human caretakers.

About research

In this study, researchers injected 15 male BFFs aged 1-4 years with SARS-CoV-2 S1 subunit vaccine mixed with alum adjuvant. A control group of nine age-matched male BFFs received only diluent and adjuvant. Fecal samples from all animals were tested before immunization to exclude enteric coronavirus infection.

Three weeks after the first injection, booster vaccines and sham injections were given to test and control groups, respectively. Vaccine doses were 50 µg based on a SARS-CoV-1 study using Syrian hamsters. Animals were observed daily for signs of illness.

Enzyme-linked immunosorbent assays (ELISA) were performed on serum samples collected from anesthetized BFFs at the time of vaccination, at the time of the booster dose, and two to three weeks and 12 weeks after the booster. Serological tests were performed to check antibody titers to SARS-CoV-2 S1 protein.

Transgenic mice expressing angiotensin-converting enzyme 2 (ACE-2) receptors were vaccinated and sera from control BFFs were administered intraperitoneally to assess whether vaccine-induced antibodies in BFFs were protective against SARS-CoV-2.

Mice were then intranasally inoculated with SARS-CoV-2 24 hours after serum transfer and were observed for signs of morbidity and weight loss. They were subsequently euthanized and tissue samples from lungs, brain, nares, spleen, liver and intestines were collected for histopathological observations.

Six BFF sets of vaccinated and unvaccinated animals also challenged SARS-CoV-2 virally. These animals were euthanized post-viral challenge and necropsied for viral titer and histopathological tests.

Results

The results reported no adverse reactions to vaccines in all 24 BFFs. Serological tests using ELISA revealed a 60-fold increase in antibody titers after the first vaccination compared to pre-vaccination levels, and a 150-fold increase after booster vaccination. However, after 12 weeks, mean titers were reduced 28-fold in all animals.

Mice receiving sera from vaccinated and unvaccinated BFFs developed an unexpected acute response to ferret serum antigen, disrupting the serum transfer and viral challenge study.

Virus-challenged BFFs did not exhibit any pathological lesions or other clinical manifestations of SARS-CoV-2, despite significant viral shedding and SARS-CoV-2 replication in the upper respiratory tract. A young BFF challenged with two inoculated viruses exhibited detectable neutralizing antibodies and shed no virus after exposure, whereas an older BFF had no detectable antibodies, indicating that age is an important predictor of antibody titer.

Although the study showed that BFFs were not susceptible to SARS-CoV-2, they demonstrated viral shedding after experimental infection, suggesting the potential for viral transmission between animals and humans. Decreased humoral response at 12 weeks also suggests the need for higher doses of vaccine.

Results

In summary, the study investigated the efficacy, safety, and immunogenicity of a candidate SARS-CoV-2 S1 subunit vaccine in captive black-footed violets to provide protection against COVID-19 in these highly threatened mammals.

The results showed that the BFFs had no adverse reactions to the vaccines and produced significant antibody responses to the immunization. The lack of clinical manifestations of COVID-19 in BFFs and the absence of SARS-CoV-2 infections in their primary prey suggest that wild BFF populations are not at risk.

However, given the close interaction between captive animals and human caretakers, the US Fish and Wildlife Service has vaccinated 60% of captive BFFs in breeding facilities.

Journal reference:

  • Leon, AE, Garelle, D., Hartwig, A., Falendysz, EA, Ip, HS, Lankton, JS, Tretten, TN, Spraker, TR, Bowen, R., and Rocke, TE (2022). Immunogenicity, safety, and antiviral efficacy of a SARS-COV-2 vaccine candidate subunit in captive black-footed ferrets (Mustela nigripes) and their susceptibility to viral challenge. Viruses. doi: https://doi.org/10.3390/v14102188 https://www.mdpi.com/1999-4915/14/10/2188

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