A new vaccine candidate construct using chimpanzee adenovirus carrying the full length of novel coronavirus spike protein is able to achieve sterilizing immunity and prevent both upper and lower respiratory tract infection in mice when administered intranasally but not when given via the intramuscular route.

  A new vaccine candidate construct using chimpanzee adenovirus carrying the full length of novel coronavirus spike protein as a transgene appears to elicit both neutralising antibodies and anti-SARS-CoV-2 immunoglobulin A (IgA) antibodies in mice models with a single intranasal dose of the vaccine. The IgA plays a crucial role in the immune function of mucous membranes. The candidate vaccine was able to confer “complete protection” against infection in both the upper and lower respiratory tracts in mice.

The very low levels of viral RNA in upper airway tissues and absence of serological response to nucleoprotein following challenge with the virus “strongly suggests” that at least some animals receiving a single dose of the vaccine administered via the intranasal route “likely achieved sterilizing immunity”. Sterilizing immunity prevents infection entirely thus preventing infection both in the upper and lower respiratory tracts in mice.

The vaccine candidate (ChAd107 SARS-CoV-2-S) when administered intranasally has the “potential to control infection at the site of inoculation, which should prevent both virus-induced disease and transmission”. “To our knowledge, none of the SARS-CoV-2 vaccine platforms currently in clinical trials use an intranasal delivery approach,” say David T. Curiel and Michael S. Diamond from Washington University School of Medicine, St. Louis, Missouri, U.S, who led the team that developed the vaccine. The results were published in the journal Cell.

No sterilizing immunity via intramuscular vaccination

However, intramuscular vaccination with either one or two doses followed by exposure to coronavirus prevented infectious virus in the lungs and substantially reduced viral RNA levels in lungs and other organs. The vaccine also “markedly reduced if not absent” lung pathology, lung inflammation, and evidence of pneumonia compared to control vaccine. However, the vaccine did not induce IgA responses or confer sterilising immunity against the virus. The researchers found detectable viral RNA levels in the lungs.

A single dose of the vaccine given intramuscular or intranasal confers “substantial and possibly complete protection” against viral replication, inflammation, and lung disease. Between the two routes of vaccination studies, the intranasal was found to be superior as it prevented upper and lower respiratory tract infection by the virus. “A single intranasal dose of the vaccine conferred superior immunity against SARS-CoV-2 challenge, more so than one or two intramuscular immunisations of the same vaccine and dose,” they write.

The greater protection observed after intranasal delivery compared with intramuscular route, the researchers speculate, is probably due to mucosal immune responses generated. They found high levels of anti-coronavirus IgA in serum and lung, and B cells secreting IgA in the spleen only when the animals were vaccinated via an intranasal route. Moreover, intranasal route of vaccination induced SARS-CoV-2-specific T cells in the lung.

Comparison with Oxford vaccine

The Oxford vaccine, which will be manufactured by India-based Serum Institute, also uses chimpanzee adenovirus vector that carries the genetic material of coronavirus spike protein. In Phase-1/2 trials, the Oxford vaccine produced neutralising antibody responses against the virus in 91% and 100% participants after one or two-dose immunisation regimens. The vaccine is administered via intramuscular route.

But in animal studies using rhesus macaques, a single dose of the vaccine given via intramuscular route prevented the animals from developing pneumonia but was unable to prevent infection in the upper respiratory tract when exposed to the virus. The vaccinated animals when exposed to virus had “significantly reduced” viral load in bronchoalveolar lavage fluid and respiratory tract tissue compared with control animals.