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Next Generation Covid Vaccine Update: Intranasal & Other Mucosal Vaxes

Cartoon of coronavirus upset at nasal spray

Mucosal vaccines are aimed at the mucosal membranes—the wet linings starting inside our noses and mouths. They can be sprays, drops, or tablets. The goal is to set up a first line of defence in those membranes, which include the lining of the lungs: mucus membranes are the entry point to our bodies for the coronavirus. That first line of defence is called mucosal immunity, and it’s backed up by systemic immunity – the antibodies and immunity-driving cells circulating in our blood. (Mucosal immunity is often called sterilizing immunity.) Some of these vaccines aim to be the total package, providing mucosal and systemic immunity, while others aim to be boosters only after shots—either an injected version of the same vaccine, or another one.

In a recent editorial, Eric Topol and Akiko Iwasaki wrote of the pandemic, “The variant-chasing strategy of an Omicron BA.1 specific or multivalent vaccine, which took more than 7 months to develop and validate after BA.1 was found to be spreading in South Africa, is not likely to provide a remedy.” Topol and Iwasaki argued that it wasn’t enough to rely only on intramuscular shots—we need tissue-level mucosal immunity to protect against infection, as well as serious Covid disease: “The only path to achieve this will be via nasal or orally administered vaccines.”

Mucosal vaccines also have the advantage of being easier to store, distribute, and use. They’re not easier to develop, though. One manufacturer, Altimmune, stopped work on theirs after phase 1 results came in, and another vaccine worked well in animals when injected, but not intranasally.

It’s been 4 months since my first post on mucosal vaccines. There are 88 mucosal vaccines in this post with preclinical and/or clinical trial results, or registered trials—16 more than in my last post—including:

  • 9 vaccines with clinical trial results;
  • Another 7 vaccines in clinical trials;
  • 8 that have reached at least phase 2 clinical trials; and
  • 5 vaccines that have also reached phase 3 efficacy trials (no increase since the last post).

The 16 new vaccines added to this post are marked with an asterisk* below.

There is still only 1 mucosal Covid vax rolled out—the Razi Cov Pars vaccine in Iran. But several vaccines have advanced. You can see lists of all the vaccines below my summary of the news. (For details on how I track Covid vaccine progress, see my background post. Notes on my collection of studies are here. The collection is in a public Zotero library you can dig into here.)

Firstly, the proof-of-concept preclinical study that Topol and Iwasaki editorialized. A group of scientists from the University of Virginia and the Mayo Clinic compared samples of blood and airway fluids of people who had been Covid-vaccinated, with those had recovered from Covid-19. They also created experimental intramuscular mRNA and intranasal adenoviral vector Covid vaxes, testing these in mice. The scientists showed that although vaxed people had at least as good signs of immunity circulating in their bloodstreams as people who had had Covid, the airway fluids showed no mucosal immunity. The mice experiments showed this pattern for mRNA vax as well, but when there was an intranasal adenoviral vax booster instead of an mRNA booster, there were signs of strong mucosal immunity response—and a strong response against Omicron, too.

Next up, there are new clinical trial results in this post for 4 vaccines, 2 each from the USA (Vaxart and Meissa) and China:

  • Vaxart’s had previously only had a press release for clinical results of their viral vector oral vaccine. They have now published a preprint of the results. Vaxart is reportedly planning a human challenge trial, where a small number of people are given the virus to test the efficacy of the vaccine. That would fast-forward final results. Vaxart has commissioned a company to develop a version of Omicron to use in that trial.
  • Beijing Wantai Biological’s influenza viral vector vaccine: new full results for their phase 1 and 2 trials were published, and there are preclinical results in mice and ferrets. This is the vaccine with the largest phase 3 trial underway, an international trial of 2 doses for 40,000 people.
  • CanSino’s adenoviral vector vaccine: there are full results now for the phase 1 and 2 trial of an aerosolized booster delivered orally after CoronaVac injection. CanSino also registered another phase 3 trial, this time for an Omicron-adapted aerosolized booster, with a planned starting date of August 1.
  • Meissa Vaccines issued a press release that I had missed in my last post. That includes some results for the first 49 participants in a phase 1 trial of their live attenuated intranasal vaccine.

There’s some news on Razi Cov Pars. That’s a 3-dose protein subunit vaccine with 2 injections plus an intranasal booster. Previously, the only results I could find were in a press release for the first participants in the phase 3 trial. There are now preclinical results for this vaccine.

Finally, some news on the Medigen protein subunit vaccine. Medigen is a manufacturer in Taiwan, and their injected Covid vaccine has authorization in Taiwan, Paraguay, and Somaliland. The injected version of this vaccine is to be evaluated by the Australian drug regulator. In early July, preclinical results for an intranasal booster after 2 shots of their vaccine were published. In late July, they released a preprint of the phase 3 trial results for the injected version.


Mucosal vaccines with clinical results

Vaccine, type, manufacturerTested useParticipantsLocation(s)Research phase
Ad5-nCoV (Convidecia)
Viral vector (adenovirus)

CanSino (China)
(All records)
2 doses aerosolized CanSino or injection or 1 injection of CanSino followed by 1 intranasal; high or low dosage.149 people.China.Phase 1. Results.
High or low dose single aerosolized dose of CanSino after 2 doses of Sinovac’s CoronaVac (inactivated vaccine); or additional dose of CoronaVac.420 people.China.Phase 1/2. Results (plus second later preprint).
Single dose aerosolized or intramuscular CanSino after 2 injections of inactivated vaccine.410 people aged 6-17 years.China.Phase 2.
Single dose aerosolized CanSino (low dosage) after 2 previous injections of inactivated vaccine (CoronaVac or Sinopharm’s Beijing or Wuhan); or 3rd injection of inactivated vaccine.10,420 people.China.Phase 3.
Single dose aerosolized or intramuscular Omicron-adapted CanSino vaccine or mRNA vaccine as a second booster after 2 injections of mRNA vaccine and an AZ booster.1,350 people.(Not stated.)Phase 3.
Single dose of aerosolized or intramuscular CanSino or injection of inactivated (CoronaVac) or protein subunit vaccine (ZF2001) as a booster after 2 injections of CoronaVac.904 people.China.Phase 4.
Single dose aerosolized or intramuscular CanSino after 3 doses of CoronaVac.360 people.China.Phase 4.
Low dose aerosolized CanSino followed by high dose intranasal.10 non-human primates (macaques).China.Preclinical. Results.
Viral vector (adenovirus)

AltImmune (USA)
(All records)
1 or 2 intranasal doses of AdCOVID (3 dosages); or placebo.92 people planned, but only 2 of 3 age cohorts recruited.USA.Phase 1Results – press release only (vax discontinued).
1 intranasal dose of AdCOVID.Mice.USA.Preclinical. Results.
Live attenuated

Codagenix (USA)
(All records)
1 dose of intranasal CoviLiv after previous course of Covid vax (2 injections of Moderna or Pfizer vax, or 1 injection of J&J), in 3 dosages.48 people.UK.Phase 1.
Press release stating successful (without data) and progressing to phase 2/3.
Results (conference abstract) and in press release.
Not yet announcedTo be powered for 150 cases of Covid-19.WHO Solidarity Trial – currently Colombia, Mali, Philippines.Announcement of joining Solidarity Trial. (Protocol.)
Viral vector (influenza)

Beijing Wantai Biological (China)
2 intranasal doses of DNS1-RBD.1,084 people.China.Phase 1.
Phase 2.
2 intranasal doses of DNS1-RBD.40,000 people.Colombia, Philippines, South Africa.Phase 3.
(Presumably 2 intranasal doses.)5,400 people.Ghana.Phase 3.
Single or 2 intranasal doses of DNS1-RBD.Mice, hamsters.China.Preclinical.
Protein subunit

Centre for Genetic Engineering & Biotechnology (CIGB) (Cuba)
(All records)
3 intranasal doses of Mambisa (drops) or 1 injection of Mambisa followed by 2 intranasal doses, each in 2 dosages & 2 different intervals.88 people.Cuba.Phase 1/2.
1 intranasal dose of Mambisa drops in 2 dosages or 1 dose of intranasal spray Mambisa, or 1 injection of CIGB’s Abdala vaccine.120 people who had recovered from Covid-19.Cuba.Phase 1/2.
Results (press release only).
1 intranasal dose of Mambisa or 1 injection of Abdala vaccine, after a previous 3-dose course of Abdala.1,500 – 5,000 people.Cuba.Phase 2.
Viral vector

Meissa Vaccines (USA)
(All records)
1 or 2 doses of MV-014-212 in one of 3 dosages, either drops or spray.130 people.USA.Phase 1.
Results (press release).
1 intranasal dose of MV-014-212 in mice.
1 intranasal and intratracheal dose of MV-014-212 in monkeys.
10 mice.
7 African green monkeys.
Viral vector (Newcastle Disease Virus)

Laboratorio Avi-Mex (Mexico)
(All records on Patria, early development of NDV-HXP-S)

2 intranasal doses of Patria, 1 intranasal dose followed by 1 injection of Patria, or 2 injections of Patria, in 3 dosages.91 people.Mexico.Phase 1.
1 intranasal or 1 intramuscular dose of Patria after previous course of Covid vax (AZ, CanSino, CoronaVac, J&J, Moderna, Pfizer, Sinopharm Beijing, or Sputnik V).396 people.Mexico.Phase 2.
Razi Cov Pars
Protein subunit

Razi Vaccine & Serum Research Institute (Iran)
(All records)
1 intranasal dose after 2 injections of Razi Cov Pars in 3 dosages, or adjuvant only.133 people.Iran.Phase 1.
1 intranasal dose after 2 injections of Razi Cov Pars, or adjuvant only.500 people.Iran.Phase 2.
1 intranasal dose after 2 injections of Razi Cov Pars, or injections of Sinopharm Beijing vaccine.41,128 people.Iran.Phase 3. (Press report of results, in the first 24,000 participants.)
1 intranasal dose after 2 injections of Razi Cov Pars.210 people (adolescents).Iran.In 12-17 year-olds.
1 intranasal dose after 2 intramuscular injections of Razi Cov Pars. Hamsters, mice, guinea pigs, rabbits.Iran.Preclinical.
Viral vector

Vaxart (USA)
(All records)
1 or 2 low-dose tablets of VXA-CoV2-1, or 1 high-dose VXA-CoV2-1 tablet.35 people.USA.Phase 1.
2 low-dose or high-dose tablets of VXA-COV2-1.1-S a month apart.896 people, either unvaccinated or mRNA-vaxed.USA.Phase 2. (Recruiting: started October 1, 2021.)
Oral VXA-CoV2-1.Mice.USA.Preclinical.
Oral VXA-CoV2-1.Macaques.USA.Preclinical.

Other mucosal vaccines – with preclinical results and/or in clinical trial

* Indicates a vaccine that wasn’t included in my previous post on intranasal vaccines.

Vaccine nameManufacturer/developerVaccine typeResearch phase
Ad5-NBeijing Institute of Basic Medical Sciences (China)Viral vector (adenovirus)Preclinical results
Ad5.SARS-CoV-2-S1University of Pittsburgh (USA)Viral vector (adenovirus)Preclinical results
Preclinical results (vaccine adapted for variant, booster)
Ad5-S-nb2Guangzhou Institutes of Biomedicine & Health & Guangzhou nBiomed (China)Viral vector (adenovirus)Preclinical results
AdC7-RBD-tr2Chengdu Kanghua Biological Products (China)Viral vector (adenovirus)Preclinical results
Preclinical results
AdCoV2-SNational Health Research Institutes (Taiwan)Viral vector (adenovirus)Preclinical results
BBV154Bharat Biotech (India)Viral vector (adenovirus)Phase 1
Phase 2
Phase 2/3
Phase 3
Phase 3
(See ChAd-SARS-CoV-2-S below for preclinical)
BCPIV/S-2PMBioComo (Japan)Viral vector (parainfluenza)Preclinical results
BReC-CoV-2West Virginia University (USA)Toxoid vector (diphtheria)Preclinical results
ChAdOx1 nCOV-19Oxford University/AstraZeneca (UK) & Serum Institute of India (Covishield) Viral vector (adenovirus)Preclinical results (ferrets)
Preclinical results (hamsters, macaques)
Preclinical results (hamsters)
Phase 1
Phase 1
ChAd-SARS-CoV-2-SPrecision Virologics with Washington University in St Louis & NIAID (USA)Viral vector (adenovirus)Preclinical results (macaques)
Preclinical results (hamsters)
Preclinical results (mice)
(See BBV154 above for clinical trials of Bharat version)
ChAdTS-S*National Institutes Food & Drug Control Beijing & West China Hospital (China)Viral vector (adenovirus)Preclinical results
CNUHV03-CA22Chungnam National University (South Korea)Live attenuatedPreclinical results
COH04S1City of Hope & NCI (USA)Viral vector (Modified Vaccinia Ankara)Preclinical results
(See records for intramuscular version of this vaccine)
CuMVTT-RBDSaiba Biotech (Switzerland)Virus-like particlesPreclinical results
CVXGA1CyanVac and University of Georgia (USA)Viral vector (parainfluenza)Phase 1
Preclinical results
Preclinical results
DelNS1-RBD4N-DAF*University of Hong Kong (China)Viral vector (influenza)Preclinical results
GAM-COVID-VAC (Sputnik V)Gamaleya Research Institute (Russia)Viral vectors x 2 (adenovirus)Phase 1/2
Phase 3 (or phase 2/3 – not clear)
GLS-5310GeneOne Life Science (South Korea)DNAPhase 1 (Trials of other versions of this vaccine)
ΔNA(RBD)-FluFred Hutchinson Cancer Research Center & University of Washington (USA)Viral vector (influenza)Preclinical results
hA5-Covid-19ImmunityBio (USA)Viral vector (adenovirus)Preclinical results
(See records for intramuscular version of this vaccine)
KaraVac*Amirabad Virology Laboratory & Pasteur Institute Tehran (Iran)Live attenuatedPreclinical results
LP18:RBDChinese Academy of Agricultural Sciences Changchun (China)Bacterium vector (Lactobacillus plantarum)Preclinical results
MigVax-101MigVax (Israel)Virus-like particlesPreclinical results
MVA-SARS-2SInstitute of Immunology Hannover (Germany)Viral vector (Modified Vaccinia Ankara)Preclinical results
MVC-COV1901Medigen (Taiwan)Protein subunitPreclinical results
(See also results for the nanoemulsion adjuvant.)
NanoSTING-NSUniversity of Houston & Auravax (USA)Protein subunitPreclinical results
Preclinical results
NDV-FLSUniversity of Guelph (Canada)Viral vector (Newcastle Disease Virus)Preclinical results
NDV-HXP-SIcahn School of Medicine Mt Sinai (USA)Viral vector (Newcastle Disease Virus)Phase 1
Preclinical results
(See records for intramuscular form of this vaccine – see also Butanvac & Patria in this post, as well as versions in Thailand and Vietnam)
NDV-HXP-S – ButanvacButantan Institute (Brazil)Viral vector (Newcastle Disease Virus)Preclinical results (See note above for the other versions of NDV-HXP-S)
NYVAC-KC-pfsSpikeArizona State University & University of Iowa (USA)Viral vector (NYVAC-KC)Preclinical results
ODN2006*National Institute of Infectious Diseases & Tokyo University of Science (Japan)Protein subunitPreclinical results
pQAC-CoVUniversity of Wisconsin-Madison & Pan Genome Systems (USA)DNAPreclinical results
rMuV-preS-6P*The Ohio State University (USA)Viral vector (mumps)Preclinical results
rNDV-SLancaster University & Texas Biomedical Research Institute (USA)Viral vector (Newcastle Disease Virus)Preclinical results (See also results for other form)
rVSVSARS-CoV-2Chinese Academy of Sciences & Shenzhen Kangtai Biotechnology (China)Viral vector (VSV)Preclinical results
SC-Ad6-1Mayo Clinic & Tetherex Pharmaceuticals (USA)Viral vector (adenovirus)Phase 1
Preclinical results
scPR8-RBD-M2BIOTEC, NSTDA & Chulalongkorn University (Thailand)Viral vector (influenza)Preclinical results
T4-CoV-2*The Catholic University of America & University of Texas (USA)BacteriophagePreclinical results
(Unnamed)Abera Bioscience (Sweden), Vrije Universiteit Amsterdam (Netherlands) & Johns Hopkins University (USA)Extracellular vesiclesPreclinical results
Errata notice
(Unnamed)Academy of Military Sciences & Chinese Academy of Sciences (China)Live attenuatedPreclinical results
(Unnamed)ACM Biolabs (Singapore)Protein subunitPhase 1
Preclinical results
(Unnamed)BioTechMed-Graz & University of Graz (Austria)Extracellular vesicles (OMV)Preclinical results
(Unnamed)FARVET, Cayetano Heredia University (Peru) Viral vector (Newcastle Disease Virus)Preclinical results
(Unnamed)Chungbuk National University (South Korea)Protein subunitPreclinical results
(Unnamed)Georgia Institute of Technology & Emory University (USA)Protein subunitPreclinical results
(Unnamed)ID Pharma & National Institute of Infectious Diseases (Japan)Viral vector (F-deleted Sendai virus)Preclinical results
(Unnamed)INSERM (France) & CONICET (Argentina)Virus-like particlesPreclinical results
(Unnamed)*Institute of Experimental Medicine St Petersburg (Russia)Viral vector (influenza)Preclinical results
(Unnamed)Intravacc (Netherlands)Extracellular vesicles (OMV)Preclinical results
(Unnamed)Jeonbuk National University (South Korea)Replicon mRNAPreclinical results (mice)
Preclinical results (mice)
Preclinical results (hamsters)
(Unnamed)Mahidol University & Institute of Biological Products (Thailand)Protein subunitPreclinical results
Preclinical results
(Unnamed)McMaster University (Canada)Viral vector (adenovirus)Preclinical results
(Unnamed)National Cancer Institute NIH (USA)Protein subunitPreclinical results
Preclinical results (booster adapted for variant)
(Unnamed)*National Engineering Research Center of Immunological Products (China)DNAPreclinical results
(Unnamed)National Institute of Allergy & Infectious Diseases (NIAID) NIH (USA)Viral vector (parainfluenza)Preclinical results
Preclinical results (pediatric primates)
(Unnamed)*National Institute of Allergy & Infectious Diseases (NIAID) NIH (USA)Viral vector (Modified Vaccinia Ankara)Preclinical results
(Unnamed)*Ohio State University (USA)Protein subunitPreclinical results
(Unnamed)Oragenics & National Research Council (Canada)Protein subunitPreclinical results
(Unnamed)*Rutgers Cancer Institute of New Jersey (USA)BacteriophagePreclinical results
(Unnamed)Shanghai Bovax Biotech & GeneSail Biotech (China)Viral vector (adenovirus)Preclinical results
(Unnamed)Sichuan University (China)Protein subunitPreclinical results
Preclinical results
(Unnamed)Stanford University (USA)DNAPreclinical results
(Unnamed)State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen (China)Viral vector (influenza)Preclinical results
(Unnamed)Sun Yat-Sen University & Chinese Academy of Sciences (China)Protein subunitPreclinical results
(Unnamed)Texas Biomedical Research Institute (USA)Live attenuatedPreclinical results
(Unnamed)TheraVectys & Pasteur Institute (France)Viral vector (Lentivirus)Preclinical results (mice)
Preclinical results (mice)
Preclinical results (mice, hamsters)
(Unnamed)University of California Los Angeles (UCLA) (USA)Bacterium vector (ΔcapB)Preclinical results
(Unnamed)University of Hong Kong (China)Protein subunitPreclinical results
(Unnamed)University of Hong Kong (China)Live attenuatedPreclinical results
(Unnamed)University of Manitoba (Canada)Viral vector (recombinant VSV)Preclinical results
(Unnamed)*North Carolina State University, University of North Carolina, & Duke University (USA)Extracellular vesiclesPreclinical results
(Unnamed)*University of North Carolina-Chapel Hill & North Carolina State University (USA)Protein subunitPreclinical results
(Unnamed)*University of Texas (USA)Viral vector (parainfluenza)Preclinical results
(Unnamed)*University of Virginia & Mayo ClinicViral vector (adenovirus)Preclinical results
(Unnamed)*University of Wisconsin-Madison (USA)Protein subunitPreclinical results
(Unnamed)Vyriad & Imanis Life Sciences (USA)Viral vector (VSV)Preclinical results
(Unnamed X 2)Yale University & Xanadu Bio (USA)Protein subunit & PACE encapsulating mRNAPreclinical results
(Unnamed)Yunnan Key Laboratory & IMBCAMS (China)PeptidePreclinical results
VSV-SARS2-EBOVNational Institute of Allergy and Infectious Diseases (NIAID) NIH & University of California Irvine (USA)Viral vector (VSV)Preclinical results (hamsters)
Preclinical results (macaques)
NYVAC-KC = a vaccinia virus; LVS ΔcapB = a live vaccine strain with a deletion in capB, from a vaccine against tularemia; OMV = outer membrane vesicles; PACE = Poly(amine-coester)s; VSV = vesicular stomatitis virus.


You can keep up with my work at my newsletter, Living With Evidence. And I’m active on Mastodon: 

For details on how I track Covid vaccine progress, see my background post. Notes on my collection of studies are here. The collection is in a public Zotero library you can dig into here.

Cartoon of facing off coronavirus

All my Absolutely Maybe Covid-19 vaccine posts

All previous Covid-19 posts at Absolutely Maybe

My posts at The Atlanticat WIRED, and debunking posts at my personal website.

Disclosures: My interest in Covid-19 vaccine trials is as a person worried about the virus, as my son is immunocompromised: I have no financial or professional interest in the vaccines. I have worked for an institute of the NIH in the past, but not the one working on vaccines (NIAID). More about me.

The cartoons are my own (CC BY-NC-ND license). (More cartoons at Statistically Funny.)

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