Orally delivered temperature-stable tablet vaccine efficacy against SARS-CoV-2 and other respiratory infections

By Shanet Susan AlexApr 14 2022Reviewed by Aimee Molineux

In a recent article published in the Vaccines journal, researchers assessed the protective efficacy of temperature-stable orally delivered vaccines against respiratory viral pathogens.

Background

Next-generation vaccines must be formulated, manufactured, and administered readily to combat the emerging viral infections, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and avert future pandemics.

Although innovative vaccines were formulated and manufactured in record time during the ongoing coronavirus disease 2019 (COVID-19) pandemic, factors such as slow distribution and storage requirements hindered rapid vaccine rollout.

Moreover, vaccine reluctance in developed countries, particularly regarding injections, stymies adequate vaccination rates. Hence, next-generation vaccines require novel strategies to prevent severe disease and infection and minimize community transmission of respiratory pathogens like SARS-CoV-2 and influenza. 

A vaccine tablet stable at room temperature, which uses a molecular toll-like receptor 3 (TLR3) adjuvant and non-replicating adenoviral vector 5 (rAd5) technique, has been developed recently. This oral rAd5 modular vaccine technology has been assessed in multiple phase I and II clinical studies, including trials for SARS-CoV-2, norovirus, and influenza, and could be used against various pathogenic viruses. 

About the study

In the present study, the researchers analyzed the mechanism of the mucosal and systemic antigen-specific responses elicited by the oral rAd5-based vaccine tablet against SARS-CoV-2 and influenza in both preclinical and clinical studies.

The researchers analyzed various types of next-generation vaccines, including oral and intramuscularly administered vaccines’ distribution, formulation, and manufacturing timelines in a pandemic. They subsequently assessed the advantages of the orally administered rAd-based vaccines relative to the intramuscularly delivered rAd-based and messenger ribonucleic acid (mRNA) vaccines. Further, the differences between the humoral and cellular responses elicited by the mucosal and parenteral vaccinations were estimated.

The authors assessed the ability of the oral rAd5 vaccine-induced mucosal humoral responses to protect against viral infection and limit transmission. The team also evaluated novel immune correlates for mucosal vaccines. Finally, the authors determined if the oral rAd-based vaccines exhibit anti-vector responses as observed in the rAd-based parenteral vaccines.

Findings

The study results illustrated that the oral rAd-based vaccine tablet could be prepared and released in <16 weeks after the antigen design is finalized and used without the requirement of a cold chain. The oral rAd5 tablet vaccine has various benefits relative to standard needle-based vaccination strategies such as triggering protective immune responses at primary infection sites.

Several preclinical and clinical assessments depicted that oral rAd5-based immunization induces T cells and antibody-secreting cells (ASCs) that display mucosal homing integrins and improve immunoglobulin A (IgA) responses specific to pathogens.

An influenza human challenge research found that combining mucosal-directed cellular and humoral responses affords increased protection against respiratory pathogens. Recent reports demonstrated that the determinants of immunity imparted by an oral rAd5 mucosal vaccine were distinct, including α4β7+ integrin and ASCs, relative to the presently authorized parenteral vaccines. 

The needle-based systemic vaccine administration has effectively established long-standing immunity to several human pathogens. However, a vaccine platform based on an oral rAd5 tablet has unique benefits over the existing parenteral vaccines, as it could be stored at room temperature, rapidly produced, and easily administered. Oral vaccination with rAd-based tablet induced mucosal antigen-specific responses and limited disease transmission to naïve animals. The anti-vector responses that hinder immunogenicity had a less significant role in orally delivered rAd vaccine tablets than the injected rAd vaccine.

Altogether, oral rAd5 vaccines were proven to be safe, immunogenic, and well-tolerated while also demonstrating a unique distribution benefit as a room temperature-stable tablet that could be self-administered and shipped globally. Hence, the deployment of an oral rAd5 tablet-based and room temperature-stable vaccine will be a game-changing technology that will significantly reduce the worldwide burden of pathogenic viral infections.

Conclusions

Overall, the study findings demonstrated that the oral vaccine based on rAd5 modular technology containing a unique molecular TLR3 adjuvant is deliverable via tablet and does not require injections. This room temperature-stable, enterically coated vaccine tablet induces strong antigen-specific IgAs in the respiratory and gastrointestinal tracts and stimulates mucosal homing adhesion molecules on circulating T and B cells.

This innovative vaccine strategy has been tested against various influenza antigens and exhibited effectiveness in both preclinical animal experiments and phase I/II clinical studies, including a human challenge investigation. The oral rAd5 vaccine platform approach is a viable new route for assisting in timely pandemic preparedness and equal vaccine distribution throughout the world.

Additionally, the authors stated that further studies evaluating multiple cellular, mucosal, and serum endpoints are required to establish the immunogenicity and identify the determinants of the oral rAd5-based mucosal vaccine tablet efficacy.