Which noninjectable coronavirus disease 2019 (COVID-19) vaccines are under development?

Updated: Sep 24, 2021
  • Author: David J Cennimo, MD, FAAP, FACP, FIDSA, AAHIVS; Chief Editor: John L Brusch, MD, FACP  more...
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Routes of vaccine administration other than injection are also undergoing development.

Table 3. Noninjectable Investigational Vaccines (Open Table in a new window)

Noninjectable Vaccine Comments
hAd5 T-cell  (ImmunityBio and NantKwest) [79]  

Vaccine targets inner nucleocapsid (N) and outer spike (S) protein, which have been engineered to activate T cells and antibodies against SARS-CoV-2, respectively. 

Phase 1/2 trial studying the safety, reactogenicity, and immunogenicity of a SC and orally administered supplement vaccine to enhance T cell based immunogenicity in patients who already received vaccine authorized for emergency use. 

Intranasal COVID-19 vaccine (Altimmune, Inc) [26]   Study terminated.  Phase 1 dose-ranging study (AdCOVID) of 1 or 2 intranasal doses in participants aged 18-55 years showed an inferior immune response compared with intranasal vaccines given to individuals with prior immunity (eg, influenza).  
VXA-CoV2-1 oral vaccine (Vaxart) [27]   Recombinant adenovirus vector type 5 (Ad5) expressing coronavirus antigen and a toll-like receptor 3 (TLR3) agonist as an adjuvant. Preliminary phase 1 trial (n = 495) showed induced CD8 T-cell responses to the viral spike protein. Neutralizing antibodies not detected in most subjects. Company is evaluating optimal dosing schedule in order to assess efficacy in phase 2 trials. 

Transdermal microneedle COVID-19 vaccines (U of Pittsburgh; U of Connecticut; Vaxess Technologies, Verndari)  [29]  

Various universities and companies are working with transdermal microneedle delivery for COVID-19 vaccines. Testing in mice produced antibodies over a 2-wk period; microneedles are made of sugar, making it easy to mass-produce and store without refrigeration.

MV-014-212 (Meissa Vaccines) [30] Intranasal live attenuated vaccine. Generates both mucosal IgA antibodies in nasal cavity and systemically circulating antibodies. The company created the SARS-CoV-2 intranasal vaccine using their existing RSV vaccine platform. Phase 1 dose-escalating study announced in March 2021.
Triple antigen oral vaccine (Oravax)  Oravax is a collaboration between Premas Biotech and Oramed Pharmaceuticals. Clinical trial planned for mid-2021. 
Oral vaccine (Esperovax)  Gained funding from BARDA for research on oral vaccine platform. 


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