Next-generation COVID-19 vaccination strategies could deliver vaccine directly to the respiratory tract

The global COVID-19 vaccination campaign has saved around 20 million lives. However, while current COVID-19 vaccines provide protection against developing severe disease, they do little to prevent infection and transmission.

Results published in the journal Nature by physician-scientists at Beth Israel Deaconess Medical Center (BIDMC) and their colleagues suggest it may be possible to improve protection against COVID-19 by administering the vaccine directly to the respiratory tract, the primary site of entry of SARS-CoV-2 infection. .

“The failure of the current generation of SARS-CoV-2 vaccines administered intramuscularly (IM) to block infection is likely related to their inability to induce robust mucosal immune responses at the portal of entry said corresponding author Dan H. Barouch. , MD, Ph.D., director of the BIDMC Vaccine and Virology Research Center.

“In this study, we demonstrated that novel immunization strategies can significantly increase mucosal immunity in non-human primates and improve protective efficacy against mucosal viral challenge.”

Barouch and colleagues gave 40 adult rhesus macaques the Ad26 COVID-19 vaccine (Janssen/Johnson & Johnson) administered intramuscularly (IM), like an injection in the arm that adults typically receive. About a year later, the animals received a booster.

Three groups received either one dose of Ad26 vaccine IM, intranasally (IN) (administered by nasal spray) or intratracheally (IT) (administered by nebulizer or inhaler). A fourth group received a dose of the bivalent mRNA vaccine (Pfizer-BioNTech) IN. A dummy group received no reminders.

When the macaques were then confronted with a high dose of virus, investigators sampled the animals’ blood, nasal and lung fluids to monitor their immune responses. They found that IT-delivered Ad26 boost provided almost complete protection against high-dose SARS-CoV-2 challenge and induced greater mucosal immunity than IN or IM.

In contrast, mRNA IN enhancement was ineffective, suggesting that improved formulations will likely be required for effective mucosal delivery of mRNA vaccines.

“Taken together, these data demonstrate that novel immunization strategies can significantly increase mucosal immunity in non-human primates and improve protective efficacy against mucosal viral challenge,” Barouch said. “These data suggest the feasibility of developing vaccines that block respiratory viral infections.”