# Eyal Raz

**Eyal Raz** is a professor emeritus of medicine at the [University of California, San Diego](https://www.edgepedia.org/university-of-california-san-diego), known for establishing immunostimulatory DNA sequences (ISS) as T helper-1-promoting vaccine adjuvants (substance added to a vaccine to boost immune response).<sup>[1](https://www.kaimm.org/abstract/2017_fall/file/cv/mini01_01.pdf)</sup><sup> • </sup><sup>[2](https://rheumatology.ucsd.edu/research/faculty-labs/raz/index.html)</sup> That adjuvant line of work reached the clinic: the CpG-based hepatitis B vaccine HEPLISAV-B is approved in the United States, the European Union, and the United Kingdom.<sup>[4](https://www.prnewswire.com/news-releases/dynavax-announces-positive-topline-phase-12-results-supporting-potential-best-in-class-shingles-vaccine-profile-302535373.html)</sup>

| Fact | Detail |
|---|---|
| Signature work | "Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants," Nature Medicine, 1997<sup>[5](https://doi.org/10.1038/nm0897-849)</sup> |
| Patent | US 6,589,940 B1 on immunostimulatory oligonucleotides, granted 2003, assigned to Dynavax<sup>[6](https://patents.google.com/patent/US6589940B1/en)</sup> |
| Recent activity | Co-author of a March 2026 Neoplasia paper on house dust mite-induced lung cancer<sup>[7](https://profiles.ucsd.edu/eyal.raz)</sup> |

## Immunostimulatory DNA sequences

His 1997 [Nature Medicine](https://www.edgepedia.org/nature-medicine) paper reported that noncoding, ISS-enriched plasmid DNAs or ISS oligonucleotides potently stimulate immune responses to coadministered antigens, acting as adjuvants that promote T helper-1 (Th1) responses.<sup>[5](https://doi.org/10.1038/nm0897-849)</sup> Mechanistically, the ISS-DNAs suppressed IgE synthesis while promoting IgG and interferon-gamma production, and initiated the production of IFN-gamma, IFN-alpha, IFN-beta, and interleukins 12 and 18, cytokines that foster Th1 responses and enhance cell-mediated immunity.<sup>[5](https://doi.org/10.1038/nm0897-849)</sup>

The active principle is the unmethylated CpG motif. A specialist overview explains that the frequency of unmethylated CpG motifs is suppressed by at least 20-fold in vertebrate DNA but occurs at the usual frequency, about 1 in 16 dinucleotides, in most bacterial and viral DNA; bacterial DNA or synthetic oligonucleotides containing bacterially derived sequences stimulate mice and humans to mount innate and then antigen-specific Th1-type responses. The terms are complementary: CpG motifs are defined structurally, ISS functionally.<sup>[8](https://doi.org/10.1385/1-59259-688-6:145)</sup> The adjuvant effect was quantifiable in a human vaccine: adding pKISS-3 or ISS phosphorothioate oligonucleotide to a commercial inactivated subunit influenza vaccine upregulated IgG antibody responses to the viral hemagglutinins threefold and eightfold, respectively.<sup>[5](https://doi.org/10.1038/nm0897-849)</sup>

## Dynavax and industry roles

His UCSD lab page dates his roles as Director and Chief Scientific Officer at Dynavax to 1997-2000.<sup>[2](https://rheumatology.ucsd.edu/research/faculty-labs/raz/index.html)</sup> The company was built on his findings, which his lab page says led to the founding of several biotech companies.<sup>[2](https://rheumatology.ucsd.edu/research/faculty-labs/raz/index.html)</sup> 

The intellectual property behind this work was patented: US patent 6,589,940 B1, "Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof," lists Raz among its inventors, is assigned to Dynavax Technologies Corp, has a priority date of June 6, 1997, was granted on July 8, 2003, and has since expired.<sup>[6](https://patents.google.com/patent/US6589940B1/en)</sup> 

## Representative work

His 2010 Nature Medicine paper, "ERK activation drives intestinal tumorigenesis in Apcmin/+ mice," showed that Apcmin/+/Myd88-/- mice, which develop few intestinal epithelial tumors, have reduced levels of phosphorylated ERK and c-myc proteins in their intestinal epithelial cells, and that a MyD88-independent activation of ERK by EGF raises pERK and c-myc levels and restores the tumor-prone Min phenotype.<sup>[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC2882530/)</sup> ScienceDaily, reporting the study, described Raz as lead author.<sup>[10](https://www.sciencedaily.com/releases/2010/05/100509144652.htm)</sup> A 2016 follow-up in [Nature Communications](https://www.edgepedia.org/nature-communications) showed that ERK5 signaling rescues intestinal epithelial turnover and tumor cell proliferation when ERK1/2 is abrogated.<sup>[11](https://www.mucosal.org/pubs_raz.php)</sup>

His lab has also applied its immunology to cancer environmental risk: work at UCSD showed that chronic exposure to house dust mite allergens promotes lung cancer development in three mouse models, via DNA damage and NLRP3/AIM2 inflammasome-driven interleukin-1 protumor environments.<sup>[3](https://orcid.org/0009-0001-2146-2963)</sup> This line continued into 2026, with a March 2026 Neoplasia paper, "Multi-omics profiling reveals microenvironmental remodeling as a key driver of house dust mite-induced lung cancer progression," listing Raz among its authors.<sup>[7](https://profiles.ucsd.edu/eyal.raz)</sup> Current projects in his laboratory address the role of [TRP channels](https://www.edgepedia.org/trp-channels) in [T cell](https://www.edgepedia.org/t-cell) and epithelial cell activation.<sup>[2](https://rheumatology.ucsd.edu/research/faculty-labs/raz/index.html)</sup>

## From bench to clinic

Dynavax's two commercial products carry the platform Raz's work founded: HEPLISAV-B, a hepatitis B vaccine approved in the United States, the European Union, and the United Kingdom for adults 18 and older, and the CpG 1018 adjuvant, used in HEPLISAV-B and in multiple adjuvanted COVID-19 vaccines.<sup>[4](https://www.prnewswire.com/news-releases/dynavax-announces-positive-topline-phase-12-results-supporting-potential-best-in-class-shingles-vaccine-profile-302535373.html)</sup> The adjuvant remains in clinical development: as of August 21, 2025, Dynavax reported that its CpG 1018-adjuvanted shingles vaccine candidate Z-1018 achieved a 100% humoral vaccine response rate at the selected dose, with immunogenicity comparable to Shingrix and lower post-injection reactions, with a part-2 trial in adults over 70 planned for the second half of 2025.<sup>[4](https://www.prnewswire.com/news-releases/dynavax-announces-positive-topline-phase-12-results-supporting-potential-best-in-class-shingles-vaccine-profile-302535373.html)</sup>
## References

1. [Curriculum Vitae, Eyal Raz M.D. (June 2017)](https://www.kaimm.org/abstract/2017_fall/file/cv/mini01_01.pdf)
2. [Eyal Raz Lab, UCSD Division of Rheumatology](https://rheumatology.ucsd.edu/research/faculty-labs/raz/index.html)
3. [Eyal Raz, ORCID record](https://orcid.org/0009-0001-2146-2963)
4. [Dynavax Announces Positive Topline Phase 1/2 Results for Z-1018 Shingles Vaccine (PR Newswire, August 21, 2025)](https://www.prnewswire.com/news-releases/dynavax-announces-positive-topline-phase-12-results-supporting-potential-best-in-class-shingles-vaccine-profile-302535373.html)
5. [Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants, Nature Medicine, 1997](https://doi.org/10.1038/nm0897-849)
6. [US Patent 6,589,940 B1, Immunostimulatory oligonucleotides](https://patents.google.com/patent/US6589940B1/en)
7. [Eyal Raz, UCSD Profiles](https://profiles.ucsd.edu/eyal.raz)
8. [Immunostimulatory DNA Sequences: An Overview (methods chapter)](https://doi.org/10.1385/1-59259-688-6:145)
9. [ERK activation drives intestinal tumorigenesis in Apcmin/+ mice, Nature Medicine, 2010](https://pmc.ncbi.nlm.nih.gov/articles/PMC2882530/)
10. [Suppressing activity of common intestinal bacteria reduces tumor growth, ScienceDaily, May 2010](https://www.sciencedaily.com/releases/2010/05/100509144652.htm)
11. [Eyal Raz publications, mucosal.org](https://www.mucosal.org/pubs_raz.php)

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*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in immunology, microbiology, and virology › Vaccinology*

*Initially written Sep 21, 2026 · Reviewed: Sep 25, 2026; Sep 30, 2026 · Edited: Sep 25, 2026; Sep 30, 2026; Oct 15, 2026 · Last review: Sep 30, 2026*

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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license