A new nasally administered Covid-19 vaccine shows greater promise in protecting patients from both Omicron infection and disease progression than traditional vaccines used throughout the pandemic. A defining feature of the Covid pandemic is the ongoing mutation of the virus to avoid our medical interventions. We may develop a drug or vaccine that neuralizes X version of the virus, but then it mutates to Y version and escapes neutralization.

This is precisely what happened with the mRNA vaccines widely used in the United States and elsewhere. When the Pfizer and Moderna vaccines were first released in Spring and Summer 2021, they boasted roughly 90% protection against progression to severe disease. However, this protection waned heavily over the following months, both due to the nature of mRNA vaccines requiring multiple follow-up doses, and the mutation of Covid-19 to more immune evasive variants.

The release of the bivalent booster in 2022 aided this regression, but only moderately. Omicron and its subsequent family of variants remain highly immune evasive thanks in part to dozens of mutations littered throughout the genome, both within and external to the well-documented spike protein.

One method of vaccine that was before never explored, however, was nasally administered mucosal respiratory vaccines. Omicron, especially later variants such as BA.4 and BA.5, is known to have higher concentrations of virus in the lungs, meaning that a nasal vaccine could yield stronger protection.

Li et al. investigated the world’s first licensed nasal vaccine, Ad5-nCoV, on a field of over 10,000 patients. Here we analyze their findings and discuss the potential impact of the nasal vaccine for the future of the pandemic.

The Chinese Ad5-nCoV nasal vaccine acts as a booster dose similar to the bivalent mRNA booster in the United States. In China, a majority of citizens received two doses of inactivated virus vaccine, a common method of vaccination for other pathogens, though not as effective for Covid-19 as the mRNA vaccines. 

Over a two month span, over 10,000 patients received the nasal booster. Of these, 210 were monitored for immunogenicity follow ups as compared to 210 who received a control of inactivated virus booster.

The researchers first note a clear negative about their vaccine. Adverse reactions to the nasal vaccine were increased (13%) as compared to the inactivated vaccine control group (7%). These reactions range from mild, such as sore throat, cough sneezing, and headache, to much less common (<1%) moderate symptoms, such as muscular weakness and myelopathy. This is to be expected with a vaccine taken through the respiratory tract as compared to intravenously.

However, the vaccine posted much improved numbers against Omicron. Four weeks after a nasal vaccine dose, the anti-BA.4/5 neutralizing antibodies were detected in 65% of participants in the immunogencity subgroup, as compared to only 2% of those in the controlled inactivated vaccine group. Not only were anti-Omicron antibodies found in more nasal vaccine patients, the average antibody titer count in the nasal vaccine group was over six-fold higher than the control.

While antibody responses are much higher in the nasal vaccine group, this does not mean that infections are completely prevented. Only 35.1% were protected from protected from infection at their 12 month follow up. The primary outcome of Covid vaccines is not to prevent infection, but to prevent progression to severe disease. In this realm, the nasal vaccine is very successful, keeping infected patients to only mild symptoms 98.1% of the time.

Furthermore, T cell responses in the nasal vaccine group were far higher than the control, suggesting the new vaccine more strongly enables adaptive immune clearance of the virus post-infection.

Taken together, the drawbacks of Ad5-nCoV are far outweighed by the advantages. A six percentage point increase in adverse reactions to the vaccine is significantly more, though the vast majority of these reactions are relatively mild, most of which are as limited as a cough or sneeze.

Considering the 32-fold increase in patients with anti-BA.4/5 antibody responses and six-fold increase in average titer, the odd cough and sneeze seems a fair trade.

As we have recommended throughout the pandemic, we should receive an additional dose of Covid-19 vaccine every three to six months, as the antibodies developed by the immune system post-vaccination wane rapidly.

The Ad5-nCoV nasal vaccine is an encouraging alternative to intramuscular vaccination, joining intradermal and inhaled administration, the latter of which may expose the oral and tracheal mucosa to antibodies. The nasal vaccine could accomplish a similar feat, adding to its value as an alternative vaccine.

Were Ad5-nCoV to become available to American citizens in the future, considering the available safety and efficacy data, we highly encourage the regular administration of the vaccine. We would also encourage stateside vaccine developers to consider a similar approach to vaccine development, as nasal vaccines may be the next great tool to fight the ongoing evolution of SARS-CoV-2.