PLOS is a non-profit organization on a mission to drive open science forward with measurable, meaningful change in research publishing, policy, and practice.

Building on a strong legacy of pioneering innovation, PLOS continues to be a catalyst, reimagining models to meet open science principles, removing barriers and promoting inclusion in knowledge creation and sharing, and publishing research outputs that enable everyone to learn from, reuse and build upon scientific knowledge.

We believe in a better future where science is open to all, for all.

Journals
More Content
PLOS BLOGS Absolutely Maybe
Browse all PLOS Blogs
Browse all PLOS Blogs

Progress for “Universal” Vaccine & More NextGen Covid Vax News (Update No 38)

Hilda Bastian Covid-19
An anxious coronavirus is saying to another infectious agent, "They're ALL out to get me..." The other answers, "They're out to get us ALL!" (Cartoon by Hilda Bastian.
Image credit
Cartoon by Hilda Bastian, CC BY-NC-ND 4.0

This month, there are phase 2 results for a self-amplifying mRNA vaccine from Japan—and that vaccine’s developers have recently completed a phase 3 trial for a version updated for recent variants. There are also some additional results from an early trial for an intranasal vaccine, and news of clinical trials for 2 others starting in Finland and the US.

There were 12 preclinical reports, too, mostly for pancoronavirus (“universal”) vaccines. Those include several for mucosal pancoronavirus vaxes. One of them targeted several coronaviruses plus influenza, bacterial infections, and a common allergen that triggers asthma as well.

After discussing the report on the Serrana trial, I have the post broken down into the usual 3 categories of next-generation vaccines (definitions below). Each section ends with an overview of vaccines in the category – and each has a link to skip over that straight to the next news section. In addition, there are some tables tracking vaccines on my personal website.

ICYMI:

  • Addendum 1: List of authorized vaccines (with countries)
  • Addendum 2: Definitions of vaccine types
  • Addendum 3: Table of mucosal vaccines in clinical trials (here—off this blog)
  • Addendum 4: Table of pancoronavirus vaccines with preclinical results (here—off this blog)

Mucosal vaccine news

This month there were some additional lab results for participants in a phase 1 trial for an intranasal vaccine, as well as 6 preclinical reports for mucosal vaccines—half of them for pancoronavirus (“universal”) vaccines. And there’s news on intranasal vaccine trials which will be recruiting participants in Finland and the US.

Phase 1 results for an intranasal booster from Guangzhou Medical University and National Laboratory (China)

NB2155 is a viral vector vaccine, based on adenovirus 5. This is the third report from a phase 1 trial for the vaccine in China. The main report is here, and another with additional lab results is here.

The new publication reports on the effects of an intranasal booster on mucosal secretory immunoglobulin (sIgA), which is key to preventing infection. The researchers identified 42 Covid-specific mucosal sIgA monoclonal antibodies, and further analyses of these suggested ways that intranasal boosting may stimulate B cells in the nasal mucosal tissue to generate immunity.

(All records in my collection for this vaccine here.)

Intranasal vaccine trial news

  • The NIAID/NIH trial for an intranasal fusion protein vaccine called BOOST-2867 is now recruiting at all 6 sites in the US: Baltimore, Nashville, Pittsburgh, San Francisco, Seattle, and St Louis. Contact details are here.
  • I have been reporting that Rokote in Finland were planning a new phase 1 trial for a new formulation of their nasal spray vaccine, after completing a phase 1 trial of the original version of this viral vector vaccine. The company has started recruiting now in Kuopio, Finland, and there is another registration record for this trial with some more details. The trial will start with 20 participants, comparing 2 different versions of the vaccine.

Preclinical reports for mucosal pancoronavirus vaccines

  • Intranasal liposomal vaccine from Stanford University (USA): This is the first report for this vaccine. It got a lot of media coverage—here’s the university press release. Instead of relying on antigens to stimulate a specific adaptive immune response, this vaccine aims to trigger the innate immune system as well—the first line of defense against infection. (The vaccine combines TLR4 agonists with ovalbumin, aiming to stimulate both adaptive and innate immune system responses.)

    The vaccine was tested in mice, including multiple challenge tests with: Beta variant of SARS-CoV-2, mouse-adapted versions of the original SARS and a bat coronavirus, common hospital-acquired infections (Staphylococcus aureus and Acinetobacter baumannii), and a common allergen causing asthma (house dust mites). At 3 months after vaccination, the developers reported strong protection against disease symptoms caused by SARS-CoV-2 as well as the other 2 coronaviruses and the 2 bacteria (S. aureus and A. baumannii). In the house dust mites challenge tests, allergic asthma was reduced in the vaccinated mice up to the 3 months’ test.

    The developers also reported on challenge tests with influenza (H1N1) in mice that had, or had not, previously been infected with the virus, and reported that both groups of mice had developed immunity. They concluded that the vaccine “elicits durable and non-specific protection against viral and bacterial pathogens, as well as allergic airway inflammation.”

    In the press release, the developers report that they hope to go to phase 1 trial to see if it works in humans. They would test a 2-dose course of intranasal vaccine.
  • Intranasal protein subunit vaccine from Sun Yat-Sen University and Guangzhou Medical University (China): This vaccine, called 3Rs-NC, was originally developed to target Covid only, and was tested in a phase 1 trial. The developers are now targeting sarbecoviruses generally, and this new report was released as a preprint last June. It includes components from 3 protein clusters found in sarbecoviruses, including one found in SARS-CoV-2. The vaccine was tested in mice, and the developers report that the vaccine protected the animals in challenge tests with Omicron and 2 bat coronaviruses. (All records for this vaccine, including earlier versions, here.)
  • Intranasal protein subunit vaccine from University of the Chinese Academy of Sciences and Wuhan YZY Biopharma (China): As with 3Rs-NC above, there have been several reports for earlier versions in this vaccine development program (here), and the new report was released last year as a preprint. The vaccine includes components from SARS, several variants of SARS-CoV-2, MERS, and seasonal human coronaviruses. The vaccine was tested in mice and hamsters in various combinations, in injected and intranasal forms. Experiments included Omicron challenge tests in mice and hamsters, as well as a transmission experiment (co-housing vaccinated and unvaccinated hamsters). Immune responses were tested up to 48 weeks. The developers concluded that the vaccine could protect against infection and illness.

Other preclinical reports

  • Intranasal viral vector vaccine from the NIAID (NIH) (USA): This is the first report I’ve seen for this vaccine. It is based on adenovirus 4. The vaccine was tested in hamsters, including challenge testing, and compared with 2 intramuscular vaccines (the Johnson & Johnson/Janssen vaccine and Moderna’s mRNA vaccine). The developers reported that only the intranasal vaccine induced mucosal immunity. Other signs of immune response were comparable or superior to the other vaccines initially, but more durable at 6 months.
  • Intranasal protein subunit vaccine from CIGB (Cuba): This is the first report I’ve seen for this vaccine. It was developed by the manufacturers of an intramuscular vaccine approved in Cuba, called Abdala, and the development of this intranasal version included some of Abdala’s ingredients. (All records in my collection for Abdala here.) The researchers tested the intranasal vaccine in mice, and reported that it stimulated immune responses to Delta and Omicron.

Skip ahead to next news category

Mucosal Covid vaccine overview

  • 5 mucosal vaccines are currently authorized for use, at least 1 in each of 6 countries. None have been authorized by a drug regulatory agency designated stringent, or listed, by WHO. However, each has been authorized by a regulator which has transitional WHO listing for vaccines.
  • 36 mucosal vaccines have reached clinical trial, although some of the vaccines are no longer in development. The vaccines that have entered clinical trials are tracked in a table below. They are mostly viral vector vaccines.
  • In addition to the 5 authorized mucosal vaccines, 6 have reached phase 2 trials, and another 2 have reached phase 2/3 trial.

Back to contents

Durable or “variant-proof” vaccines

This month, there were reports from 2 clinical trials, with another trial starting for the self-amplifying mRNA vaccine that has been approved in Europe and Japan. There were also preclinical reports for another 2 vaccines.

Phase 1 results for an mRNA-VLP vaccine from AstraZeneca

Last month, I reported on some results for this trial in a conference abstract. There were 2 versions of the vaccine based on components of Omicron fused to Helicobacter pylori (H. pylori) ferritin protein, in 2 dosages. One version was compared to an Omicron-updated version of the BNT/Pfizer vaccine. The version named AZD6563 had a lower rate of adverse effects and better immune response than the other (AZD9838). The 10 μg dose of AZD6563 showed similar immunogenicity to the 30 μg dose of the BNT/Pfizer vaccine up to the 6 months reported so far.

The new report includes detailed data on adverse reactions. The rate of some types of adverse reactions was lower for the AstraZeneca vaccine—pain at the injection site and muscle aches—with similar rates of other reactions for the 10 μg dose and BNT/Pfizer vaccine. No safety concerns were identified.

All records for this vaccine here.

Phase 2 results for self-amplifying mRNA vaccine from VLP Therapeutics Japan

This new report of clinical trial results is for the second version of the VLPCOV vaccine program (VLPCOV-2). VLPCOV-1 was based on the original strain of SARS-CoV-2, and VLPCOV-2 was adapted for the Gamma variant. Results for phase 1 of the phase 1/2 trial of a VLPCOV-2 booster were published in 2024.

Phase 3 trials for later versions of this vaccine have been completed (VLPCOV-4, which was adapted for Omicron XBB.1.5, and VLPCOV-5). The largest and most recent is for VLPCOV-5: Vaccination was completed for 6,200 participants in that placebo-controlled booster trial by August 2025. VLP Therapeutics also reports a pan-coronavirus version in their pipeline, which is apparently gearing up for phase 1 trial.

Back to the new phase 2 results. The developers were aiming to determine an optimal dose for the vaccine, and compare its adverse effects and immune responses with the BNT/Pfizer vaccine. In 2023, 323 people were randomized to 3 μg or 7.5 μg of VLPCOV-2, or to the standard 30 μg of BNT/Pfizer vaccine (bivalent: wild-type/omicron BA.4-5).

Adverse reactions of the lower dose were similar to those of the BNT/Pfizer vaccine, and higher for 7.5 μg of VLPCOV-2. Signs of immune response for the lower dose were similar to the BNT/Pfizer vaccine up to the 1 year follow-up, with responses from all 3 vaccines waning across that time—even though the BNT/Pfizer vaccine had been updated for Omicron and VLPCOV had not.

(All records in my collection for this vaccine here.)

New trial in immunocompromised participants for the Arcturus self-amplifying mRNA vaccine, Kostaive

A new trial has been registered for this vaccine in Seattle. It is a phase 2 trial planning to compare it to the BNT/Pfizer mRNA vaccine in 56 people who have received a hematopoietic cell transplant (HCT). Eligible participants have had HCT in the last year, but no Covid vaccination. Contact details here.

Preclinical reports

  • mRNA vaccine from the Korea Disease Control and Prevention Agency Cheongju (South Korea): This is the first report for this vaccine, which incorporates components in Delta and Omicron variants. It was tested in mice, including challenge tests for the original strain of SARS-CoV-2, as well as the Delta variant and 2 types of Omicron. Mice were also tested for signs of immune response to that range of virus strains.
  • Protein subunit vaccine from the State Key Laboratory of Virology and Biosafety, Wuhan (China): This is the first report for this vaccine. It incorporates multiple components, including an adjuvant, and it was tested in mice. The developers tested versions of the vaccine for signs of immune response to the original strain of SARS-CoV-2, as well as Delta and Omicron variants. They also reported on challenge tests with the original strain and Omicron variants.

Skip ahead to next news category

Durable or “variant-proof” vaccine overview

Note: This is a rather vague category, including vaccines that aim to be more durable. I’m not sure how many can be classified as aiming to be “variant-proof”.

Authorized vaccine:

There is 1 authorized vaccine in this category, and it has been authorized by several drug regulatory authorities designated by WHO has stringent, and tested against an mRNA vaccine (Kostaive):

  • LUNAR-COV19 (USA), trade name Kostaive: This self-amplifying mRNA vaccine was authorized in Japan in November 2023, with rollout in October 2024. It was authorized for Europe in February 2025, and in the UK in January 2026.

Back to contents

Pancoronavirus vaccine news

This month, there were 8 preclinical reports for “universal” coronavirus vaccines, including 3 mucosal vaccines already included in the mucosal vax section above.

Preclinical reports

  • DNA and viral vector vaccine combination from the Changping Laboratory (China): This is the first report for this vaccine regimen, with a DNA prime and Vaccinia virus TianTan-based boost (VTT). It includes components from SARS-CoV-2, the original SARS, and MERS. It was tested in mice, and elicited signs of immune response to all 3 diseases. The developers reported that it provided protection in a challenge test with the XBB Covid variant.
  • Protein subunit vaccine from Mynvax Private (India): Mynvax previously developed a Covid vaccine. A new vaccine was developed with several versions, using combinations of components from the original SARS, SARS-CoV-2, and several animal sarbecoviruses. In a preprint last year, the developers reported on tests in mice, some of which had been pre-vaccinated with Covid vaccine. That was recently published in a journal. The mice showed signs of immune response to several coronaviruses. A detailed thesis on the development of this vaccine has now been published. (All records on the Mynvax vaccines here.)
  • DNA and protein subunit vaccine NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing (China): This is the first report for this vaccine. The vaccine was developed by evaluating a range of clade 1 and 3 sarbecoviruses to determine a group of vaccines that might be able to provide protection against sarbecoviruses generally. They developed a trivalent vaccine targeting a strain of the original SARS (SZ1), SARS-CoV-2 (D614G variant), and a pangolin strain of SARS-CoV-2 (PCoV-GX). The developers tested a regimen of DNA prime and 2 boosters of protein subunit vaccine in guinea pigs, using pseudovirus neutralization assays to test for immune responses to several Clade 1 and 3 sarbecoviruses.
  • Peptide and protein subunit vaccines from the University of Science and Technology of China, Heifei (China): This is the first report for these vaccines. Based on components of SARS-CoV-2, each of the vaccines were tested in mice. In addition, mice primed with inactivated vaccine were given the protein subunit vaccine boost, and challenged with the original strain of SARS-CoV-2, the KP.2 variant, or another human coronavirus (HCoV-229E). The developers concluded that this provided protection against each of the coronaviruses.
  • Fusion protein vaccine from the Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan (Canada): This is the second preclinical report for this vaccine. The first was for a version of the vaccine aimed at Covid variants (here). Four new versions of the vaccine targets components in Clade 1a, Clade 1b, and Clade 3 sarbecoviruses, and were tested in mice and hamsters. This included challenge tests with the Delta variant and a strain of the original SARS in hamsters. The developers concluded that the vaccines provided protection against other coronaviruses than the ones they targeted.

    Pancoronavirus vaccine overview

    A table below this post keeps track of vaccines I’ve added to this category so far that have publicly available preclinical results. Of these vaccines, 8 have reached phase 1 clinical trials, and 1 has reached phase 2. Some of them have results, and they are marked *:

    • * CoronaTcP (Gylden Pharma, UK/US) – protein subunit. (Note: This vaccine was previously called PepGNP-SARSCov2, and the manufacturer was previously called Emergex.)
    • DIOSynVax (Cambridge University spin-off, UK) – mRNA.

    • Duke University (USA) – protein subunit.

    • INSERM/Ennodc (formerly LinkInVax) (France) – protein subunit.

    • Osivax (France) – protein subunit.

    • SK Bioscience (South Korea) – protein subunit.
    • * VBI Vaccines (Canada) – eVLP. [This company announced bankruptcy in late 2024.]
    • * Walter Reed Army Institute of Research (WRAIR, USA) – protein subunit.

    Back to contents

    Addendum 1: List of authorized next generation Covid vaccines (with countries)

    There are 7 next-generation Covid vaccines authorized in 7 countries. Only one has been approved by drug regulatory agencies designated stringent, or listed, by WHO – in bold; the others have all been approved in at least one country by a drug regulator WHO has listed with transitional status for vaccines. I’ve listed the vaccines in 2 categories, in order of date of first authorization (or initial approval).

    Mucosal:

    • Razi-Cov Pars (Iran), intranasal protein subunit vaccine: Iran (October 2021).
    • Sputnik (Russia), intranasal viral vector vaccine: Russia (April 2022).
    • Convidecia (China), inhaled viral vector vaccine: China (September 2022), Morocco (November 2022), Indonesia (March 2023).
    • iNCOVACC (USA/India), intranasal viral vector vaccine: India (September 2022).
    • Pneucolin (China), intranasal viral vector vaccine: China (December 2022).

    Durable or “variant-proof”:

    • Gemcovac (India), self-amplifying mRNA vaccine: India (June 2022).

    Back to contents

    Addendum 2: Definitions of vaccine types

    • Mucosal vaccines: These enter the body the way the virus does – through mucosal tissues. It’s hoped that provides defence against infection. They can be administered via different routes – squirts or drops in the nose, inhaled through the mouth through a nebulizer (similar to an asthma medication), or in tablet, capsule, or sublingual form.
    • Pan-SARS-CoV-2 or “variant-proof” vaccines: These aim to provide protection against any variant of the coronavirus that causes Covid-19.
    • Pancoronavirus vaccines aim to protect against coronaviruses more broadly – sometimes called “universal coronavirus vaccine.” These vaccines can be targeted to:

      – the “subgroup” the 2 SARS viruses came from (the sarbecovirus subgenus),

      – coronaviruses from the next level up (the genus, betacoronavirus, which includes MERS as well as the sarbecoviruses), or

      – up to the whole coronavirus family, which has 4 genuses, including betacoronavirus and alphacoronavirus (with more common cold viruses).

      I classify a vaccine as a pancoronavirus one when the developers are explicitly targeting coronaviruses more broadly than SARS-CoV-2 in the design of the vaccine, and have tested for signs of response to non-SARS-CoV-2 coronavirus(es) (or clearly plan to).

    Back to contents

    You can keep up with my work at my newsletter, Living With Evidence. And I’m active on Mastodon: @hildabast@mastodon.online and less so on BlueSky (hildabast.bsky.social).

    ICYMI:

    ~~~~

    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.

    Previous update posts specifically on next generation Covid vaccines prior to this monthly series (beginning May 2023):

    1. Mucosal vaccines (March 2022)
    2. Pan-SARS-Cov-2 and pancoronavirus (July 2022)
    3. Mucosal vaccines (July 2022)
    4. Mucosal vaccines (September 2022)
    5. Mucosal vaccines (April 2023)
    6. Pancoronavirus vaccines (April 2023)

    All my posts on Covid vaccines, beginning from March 2020, are tagged here.

    All previous Covid-19 posts at Absolutely Maybe

    My posts at The Atlantic and at WIRED.

    Disclosures: My interest in Covid-19 vaccine trials began as a person worried about the virus, as my son was 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 one working on vaccines. More about me.

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

    Postscript: US Project NextGen funded trials

    Mucosal vaccines:

    • Phase 1 for MPV/S-2P, the intranasal viral vector vaccine developed by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). This trial for 60 participants began recruiting in July 2024, and finished recruiting by early 2025.
    • Phase 2b for the oral viral vector vaccine from Vaxart (trial start announced at the end of September 2024; trial registration here) – further recruitment for this trial was cancelled, though followup will be completed for the participants already dosed (around 5,000). The company has a deal with Dynavax to take the vaccine forward, depending on phase 2 trials.
    • Phase 2b for the intranasal viral vector vaccine from CyanVac/Blue Lake Biotech (trial started in December 2024, trial registration here) – no recent news on this trial.
    • 2 trials are apparently not going ahead: A Phase 2b (“mini-efficacy”) for the intranasal protein subunit vaccine from Castlevax – this grant was paused and may be terminated. Castlevax has since registered a far smaller phase 2a trial with some similar methodological features. Another for the intranasal live attenuated vaccine from Codagenix had not apparently started.

    Durable or “variant-proof” vaccines:

    • Phase 1 for TNX-1800 from Tonix (aiming for lifelong immunity) (planned to go into clinical trial in 2024 – no recent news);
    • Funding was terminated for the Phase 2b (“mini-efficacy”) trial for GeoVax (viral vector vaccine).

    Note: Gritstone Bio was originally in line for a phase 2b trial for their self-amplifying mRNA vaccine. However, the company declared bankruptcy and in January 2025, their assets were sold.

    Pancoronavirus vaccines – presumed canceled:

    • CoronaTcP (Gylden Pharma, UK/US) – protein subunit.
    • Unnamed (PopVax, India) – mRNA.

    Back to contents

    Leave a Reply

    Your email address will not be published. Required fields are marked *


    Add your ORCID here. (e.g. 0000-0002-7299-680X)

    Related Posts
    Back to top