# AddaVax, AddaS03, and Alum Effectively Enhance Cross-Reactive and Cross-Neutralizing Antibody Responses Against SARS-CoV-2 Induced by the Inactivated NDV-HXP-S Vaccine in Mice

**Authors:** José Luis Martínez-Guevara, Tsoi Ying Lai, Mitali Mishra, Stefan Slamanig, Irene González-Domínguez, Adam Abdeljawad, Minh Thu Hoang, Gagandeep Singh, Shreyas Kowdle, Benhur Lee, Florian Krammer, Peter Palese, Weina Sun

PMC · DOI: 10.3390/vaccines14020138 · Vaccines · 2026-01-29

## TL;DR

This study shows that adding specific adjuvants to a SARS-CoV-2 vaccine boosts antibody responses in mice, potentially improving vaccine effectiveness and reducing costs.

## Contribution

The study identifies AddaVax, AddaS03, and Alum as effective adjuvants for enhancing immune responses to a SARS-CoV-2 vaccine in mice.

## Key findings

- AddaVax, AddaS03, and Alum induced strong IgG responses to the ancestral spike protein.
- These adjuvants boosted cross-reactive antibodies against S1 and S2 subunits and elicited high cross-neutralizing titers.

## Abstract

Background/Objectives: We previously developed a low-cost vaccine based on Newcastle disease virus expressing a stabilized pre-fusion spike of SARS-CoV-2 (NDV-HXP-S), which has shown safety and immunogenicity in pre-clinical and clinical studies. Due to the emergence of immune-evasive variants and the need to protect vulnerable populations, we evaluated adjuvanted NDV-HXP-S vaccine formulations to enhance and broaden immune responses. Methods: We tested the antibody responses of mice immunized intramuscularly with an inactivated NDV-HXP-S vaccine adjuvanted with AddaVax, AddaS03, Alhydrogel adjuvant 2% (Alum), or Quil-A. Results: AddaVax, AddaS03, and Alum induced the strongest IgG responses to the ancestral spike protein, boosted cross-reactive antibodies against both S1 and S2 subunits, and elicited high cross-neutralizing titers. Conclusions: The present results highlight the critical role of adjuvant selection in shaping both the magnitude and breadth of the immune response induced by the NDV-HXP-S vaccine. AddaVax, AddaS03, and Alum stand out as promising candidates to enhance NDV-HXP-S vaccine immunogenicity, with potential applications in booster strategies against SARS-CoV-2, enabling dose sparing and reducing costs.

## Linked entities

- **Proteins:** CHMP5 (charged multivesicular body protein 5), PSMD1 (proteasome 26S subunit, non-ATPase 1), PSMD2 (proteasome 26S subunit ubiquitin receptor, non-ATPase 2)
- **Chemicals:** AddaVax (PubChem CID 1105), Quil-A (PubChem CID 56841866)
- **Diseases:** SARS-CoV-2 (MONDO:0100096)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, S (surface glycoprotein) [NCBI Gene 43740568] {aka spike glycoprotein}, FUZ (fuzzy planar cell polarity protein) [NCBI Gene 80199] {aka CPLANE3, FY, NTD}
- **Diseases:** malaria (MESH:D008288), bleeding (MESH:D006470), RECOMBINANT (MESH:C535296), infection (MESH:D007239), pandemic (MESH:D000086382), injury to (MESH:D014947), viral infection (MESH:D014777)
- **Chemicals:** Tween-20 (MESH:D011136), hydrochloric acid (MESH:D006851), saponin (MESH:D012503), BPL (MESH:D011420), water (MESH:D014867), BA.1 (MESH:C006646), MF59 (MESH:C089950), bicinchoninic acid (MESH:C047117), ketamine hydrochloride (MESH:D007649), Quil-A (MESH:C046386), CO2 (MESH:D002245), sucrose (MESH:D013395), aluminum hydroxide (MESH:D000536), QS-21 (MESH:C078785), Alum (MESH:C041524), xylazine (MESH:D014991), AddaVax (MESH:C000590912), o-phenylenediamine dihydrochloride (MESH:C034193), AS03 (MESH:C550253), Oil (MESH:D009821), streptomycin (MESH:D013307), Alhydrogel adjuvant (-), proline (MESH:D011392), disodium phosphate (MESH:C018279), penicillin (MESH:D010406)
- **Species:** Gallus gallus (bantam, species) [taxon 9031], Vesicular stomatitis virus (species) [taxon 11276], Severe acute respiratory syndrome-related coronavirus (no rank) [taxon 694009], Newcastle disease virus [taxon 11176], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Mus musculus (house mouse, species) [taxon 10090], Quillaja saponaria (species) [taxon 32244], Homo sapiens (human, species) [taxon 9606], Felis catus (cat, species) [taxon 9685], Vibrio sp. A-C (species) [taxon 640641]
- **Mutations:** EF156-157del, L18F, E484K, R246I, T478K, D614G, K986P, V987P, R158G, 242-244del, D215G, L452R, C with 50, T19R, D80A, N501Y, A942P, A701V, A899P, G142D, 80  C, K417N, A892P, F812P, P681R
- **Cell lines:** hACE2 — Homo sapiens (Human), Transformed cell line (CVCL_C1G1), BHK — Mesocricetus auratus (Golden hamster), Spontaneously immortalized cell line (CVCL_1914), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12945119/full.md

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12945119/full.md

## References

57 references — full list in the complete paper: https://tomesphere.com/paper/PMC12945119/full.md

---
Source: https://tomesphere.com/paper/PMC12945119