A study in Microbiology Spectrum in March 2023 demonstrated the benefits of an oral vaccine for COVID-19 that could “dramatically improve immunisation rates”. The universal vaccine is based on the nucleocapsid protein, which evolves at a slower rate than the spike protein. It exploits a weakened bacterium to produce the nucleocapsid protein and membrane protein in infected cells. Tested in hamsters, the vaccine displayed safety and potency. 

Continuing the fight against SARS-CoV-2 

The authors note that the COVID-19 pandemic, caused by SARS-CoV-2, has (at time of writing), caused over 585 million cases and over 6.4 million deaths worldwide. In a worldwide vaccination campaign that varies “widely”, approximately 60% of the global population has been vaccinated. However, vaccination rates are much lower that this in many places.  

Although the available vaccines have been “highly successful” in reducing the effects of infection, variants are “continuously emerging” to render them “less and less effective”. Most are centred on responses to the Spike (S) protein. The paper identifies one approach to this problem as “redesigning and testing new vaccines” in response to circulating variants. This means essentially opting into a game of catch up against a virus, and current vaccines quickly become “obsolete”, says Dr Marcus Horwitz of UCLA. The researchers suggest that in order to tackle the pandemic “most effectively”, we really need “universal vaccines”.  

“The optimal COVID-19 vaccines would be safe, potent, and affordable, as well as universal.” 

The candidate in question 

The researchers believes that their vaccine, which comprises a replicating bacterial vector expressing the SARS-CoV-2 membrane (M) and nucleocapsid (N) proteins, fulfils these criteria. They break down each criterion as follows. 

  • Safety – the vaccine vector is a further attenuated version of a tularemia vaccine, which has been administered to “millions” of people. 
  • Potency – two immunisations of the MN vaccine have been demonstrated to protect golden Syrian hamsters after “high-dose SARS-CoV-2 respiratory challenge”. 
  • Affordability – the vaccine can be grown to “hundreds of millions of doses overnight” in a “simple broth culture”. Furthermore, after lyophilisation, it can be stored and transported at “refrigerator temperature”.  
  • Universality – the MN vaccine is centred on inducing immunoprotective humoral and T cell responses to “highly conserved SARS-CoV-2 proteins”.  

Another feature of the vaccine is capability for oral administration, which would address “two major factors hampering more all-inclusive vaccination”. The first is a lack of equipment and “trained personnel” to deliver injectable vaccines. The second is a “contributing, albeit difficult to quantitate” factor to vaccine hesitancy: feat of needles. This would be “rendered moot” by oral delivery.  

The study 

The study advances previous research to demonstrate the efficacy of this vaccine when administered orally, as opposed to intradermally or intranasally. The results suggest that it prevented against “severe weight loss” and protection was “at least as strong” as with other methods of administration. It also “significantly protected against lung pathology” and “significantly reduced the viral load in the oropharynx and lungs”.

The authors believe that their “highly demanding animal model” is a positive indication of the potential presented by their vaccine.  

“This conveniently administered, easily manufactured, inexpensive, and readily stored and transported vaccine could play a major role in ending the COVID-19 pandemic by protecting immunised individuals from serious disease from current and future strains of SARS-CoV-2.” 

Next steps 

Dr Horwitz hopes that the vaccine will progress to manufacturing for oral administration through an acid-resistant enteric capsule. This would allow it to be safely released in the small intestine, and it could then be tested in humans. 

“We also plan to expand the vaccine to protect against infections caused by other types of potentially pandemic coronaviruses such as the virus that causes Middle Eastern Respiratory Syndrome.”  

This could be a helpful tool in our continued fight against the constantly evolving virus. Do you think an oral vaccine is the solution? Will it help us overcome elements of vaccine hesitancy? 

For more on COVID-19 vaccine strategies at the World Vaccine Congress in Washington next month, get your tickets here.