the future of covid vaccines? look to the nose

seventy years ago, polio had parents around the world  trembling in fear . the highly infectious poliovirus paralyzed thousands of children before  two vaccines  emerged – one injected through the arm and the other taken orally.

like many other children, ulrich von andrian was given the oral vaccine – a few drops of weakened poliovirus on a sugar cube. this vaccine  built up  defenses in his intestines, where the virus first infects the body and replicates, protecting against initial infection in the gut lining.

while the intramuscular polio vaccine defends against paralysis, it is  less effective  at stopping virus replication in the gut and protecting unvaccinated individuals from infection. the oral vaccine was critical in bringing the polio pandemic under control because it  reduced transmission .

the  nose  is the first line of defence for the coronavirus, much like the gut is for the poliovirus. currently, covid-19 vaccines are injected into the muscles but many immunologists think a nasal vaccine may also be  needed  to end the pandemic. like the oral polio vaccine, it could  offer  local protection – right at the source.

both the inner nose and gut are covered in mucosa – a moist tissue lining that protects exposed areas from outside invaders. it produces special  mucosal  antibodies designed to neutralize viruses before they can spread to the rest of the body. these mucosal antibodies are  extra effective  against the coronavirus –  7.5 times more effective  than normal antibodies according to some estimates.

intramuscular vaccines typically  do not stimulate powerful  mucosal immune system responses. but the immune response to mrna vaccines is a new field of study. a recent  preprint analysis  of the pfizer and moderna vaccines suggests that they may stimulate the production of mucosal antibodies, and  preliminary data  from israel suggest the pfizer vaccine reduces viral load fourfold.

while the risk of transmission is still being investigated in humans, animal models – including experiments with  non-human primates  – show that the coronavirus still replicates in the nose after vaccination, though likely at a  reduced rate , says michael diamond, an immunologist at washington university.

so while vaccinated individuals are  less likely to harbour and transmit the virus , they still may be able to spread it to others. this is partly why health officials recommend vaccinated individuals  continue wearing masks  even after getting the jab. furthermore, any continued replication presents the risk of not only more covid-19 cases, but also new mutations.

immunologists at the university of buffalo  argue  that mucosal immunity should be central to future vaccine efforts. as the largest part of the immune system, the mucosa needs to be directly stimulated and recruited to defend against the coronavirus, they say.

michael diamond has recently used a single-dose nasal vaccine to successfully  cut off the virus  at the point of entry in mice. his team found that nasal delivery stimulated a strong immune response throughout the body, particularly in the upper respiratory system. “we have to wait and see what its efficacy is on humans,” he says.

unlike the influenza vaccine administered through the nose, this intranasal vaccine doesn’t use a live virus to stimulate immunity. instead, it uses a modified adenovirus to carry the coronavirus spike protein into the nose ,  which  should be safer .

many biopharmaceutical companies  have just started human trials on nasal covid-19 vaccines. while these will  take time , bharat biotech says they may provide  better mucosal immunity  and increase vaccination willingness among both kids and adults. nasal sprays could also be easier to store at room temperature, administer without medical training, and dispose of without needle pollution.

in the effort to create global immunity, the intranasal vaccine may be particularly important in  low-resource settings . anything that is more stable than current mrna vaccines could target a wider audience, says jennifer dan, an infectious disease specialist at the university of california, san diego. “it’s a good idea to try any method to get a good immune response to prevent infections,” she adds.

both types of vaccines  were ultimately needed to stop the poliovirus. the intramuscular polio vaccine is better than the oral vaccine at protecting vaccinated individuals, so it remains the most popular polio vaccine. but the oral polio vaccine is still used by the  world health organization eradication program  to reduce spread in countries with wild polio.