Vaccine News: COVID-19 Intramuscular Vaccination Does Not Prevent Susceptibility To SARS-CoV-2 Infection Of The Upper Respiratory Tract

Vaccine News: A new vivo animal study by scientist from Pennsylvania State University shows that intramuscular COVID-19 vaccination of ferrets failed to induce sufficient antibodies against SARS-CoV-2, and the ferrets remained susceptible to infection of the upper respiratory tract. The study shows that protection of upper respiratory tract will require vaccines that mimic natural infection by SARS-CoV-2.


 
Utilizing the reference strain SARS-CoV-2 USA-WA1/2020, (The SARS-CoV-2 USA-WA1/2020 strain is a CDC reference strain used by multiple research laboratories ever since Thailand Medical News lobbied for all research studies to include mentioning of SARS-CoV-2 strains used in any drug, therapeutic and vaccines studies), the study team evaluated modes of transmission and the ability of prior infection or vaccine-induced immunity to protect against infection in ferrets. Ferrets were semi-permissive to infection with the USA-WA1/2020 isolate. When transmission was assessed via the detection of vRNA at multiple timepoints, direct contact transmission was efficient to 3/3 and 3/4 contact animals in two respective studies, while respiratory transmission was poor to only 1/4 contact animals.
 
To assess the durability of immunity, ferrets were re-challenged 28 or 56 days post-primary infection. Following viral challenge, no infectious virus was recovered in nasal wash samples. In addition, levels of vRNA in the nasal wash were several orders of magnitude lower than during primary infection, and vRNA was rapidly cleared.
 
In order to determine if intramuscular vaccination protected ferrets against infection, ferrets were vaccinated using a prime-boost strategy with the S-protein receptor-binding domain formulated with an oil-in-water adjuvant.
 
Significantly upon viral challenge, none of the mock or vaccinated animals were protected against infection, and there were no significant differences in vRNA or infectious virus titers in the nasal wash.
 
The study findings demonstrates that in ferrets direct contact is the predominant mode of transmission of the SARS-CoV-2 USA-WA1/2020 isolate and immunity to SARS-CoV-2 is maintained for at least 56 days. The study findings also indicate protection of the upper respiratory tract against SARS-CoV-2 will require vaccine strategies that mimic natural infection or induce site-specific immunity.
 
The study findings were published on a preprint server and are currently being peer reviewed. https://www.biorxiv.org/content/10.1101/2020.11.20.392381v1
 
The SARS-CoV-2 coronavirus crossed the species barrier and started infecting humans in Wuhan, China, in late 2019. The unprecedented global pandemic initiated by SARS-CoV-2 has prompted scientists to work on developing a preventive vaccine urgently.
 
The novel coronavirus is predominantly transmitted via respiratory droplets. It causes a range of symptoms such as fever, cough, and shortness of breath in most people. In some people, the infection can lead to severe pneumonia, hospitalization, and mortality.
 
Numerous SARS-CoV-2 virus isolates have been taken from infected patients to characterize SARS-CoV-2 and develop vaccines or drugs to fight infection. One such isolate obtained from a patient who traveled to the US from China, SARS-CoV-2 USA-WA1/2020, is widely used in SARS-CoV-2 research.
 
Many animal models of SARS-CoV-2, including hamsters, transgenic mice with the human ACE2 receptor, cats, and ferrets, have also been developed for research purposes. Ferrets are an established model of influenza transmission and immunity, and the efficacy of the influenza vaccine in ferrets correlates with the efficacy of the vaccine in humans.
 
Although several intramuscular SARS-CoV-2 vaccine candidates are in various phases of clinical trials and some are in the midst of seeking regulatory approvals, it is not clear if they will offer protection against SARS-CoV-2 infection despite the carefully manipulated and non-clear findings that have been disclosed by some recently.
 
The study team from the Pennsylvania State University and the Emory-UGA Center of Excellence of Influenza Research and Surveillance (CEIRS) studied the transmission modes of SARS-CoV-2 and the protection against re-infection in ferret models and examined the modes of transmission and if immunity acquired through a prior infection or vaccination can protect ferrets against infection.
 
The study team found that the ferrets were semi-permissive to infection by the SARS-CoV-2 USA-WA1/2020 isolate. On assessing transmission at multiple time points through the detection of vRNA, direct contact transmission was found in 3/3 and 3/4 contact animals in 2 respective studies, while the respiratory transmission was detected in only 1/4 contact animals.
 
To assess the durability of immunity, the experiment was repeated in the ferrets 28 or 56 days after primary infection. Following re-challenging with the viral isolate, no infectious virus was found in the nasal wash samples of the ferrets. Moreover, vRNA levels in the nasal wash were several folds lower than that detected during primary infection, and the vRNA also cleared rapidly.
 
The results showed that intramuscular vaccination with SARS-CoV-2 S protein RBD did not offer protection against infection in ferrets.
 
The study team then used a prime-boost strategy and vaccinated the ferrets with the S-protein receptor-binding domain formulated as an oil-in-water adjuvant to determine if intramuscular vaccination offered protection against infection. Upon viral challenge, none of the vaccinated animals had protection against infection, and no significant differences were found in the vRNA levels or infectious virus titers in the nasal wash of the ferrets.
 
The study findings demonstrate that direct contact is the primary mode of transmission of the SARS-CoV-2 USA-WA1/2020 strain in ferrets and SARS-CoV-2 immunity is intact for at least 56 days. The study also indicates that only vaccine strategies mimicking natural infection or inducing site-specific immunity can offer protection of the upper respiratory tract against SARS-CoV-2.
 
The study team shows that direct contact is the predominant transmission mode of this SARS-CoV-2 strain in ferrets. They further demonstrate that ferrets had protection against re-infection even when neutralizing antibody levels were low or undetectable.
 
The study findings also showed that intramuscular vaccination of the ferrets failed to induce sufficient antibodies against SARS-CoV-2, and the ferrets remained susceptible to infection of the upper respiratory tract. In conclusion, these studies suggest that in order to protect the upper respiratory tract, we require vaccines that mimic natural SARS-CoV-2 infection.
The study team hopes that although initial human vaccines can help reduce disease burden, in order to prevent SARS-CoV-2 infections fully, vaccines that can induce immunity in the upper respiratory tract just like the natural infection will need to be developed.
 
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