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Microbes & Immunity Advax-adjuvanted typhoid vaccine

Typhax vaccine efficacy as compared to traditional large Acknowledgments
phase 3 outcome studies that seek to assess vaccine impact
on spontaneous natural infections. 54 We wish to thank all the Vaxine and Matrivax research
team members who contributed to the review of this paper.
7. Future directions Funding
Parenteral typhoid fever vaccines have evolved from pure Vi The writing of this paper was supported in part by
polysaccharide vaccines to protein-conjugated Vi vaccines
that provide better helper T-cell response and result in the National Institutes of Health, National Institute
of Allergy and Infectious Diseases, USA (grand no.:
higher and more durable Vi antibody levels, thereby HHSN272200800039C, HHSN272201400053C, and
extending protection. The application of conjugation HHSN272201800044C). The paper’s contents are solely
technology to typhoid vaccines represented a significant the responsibility of the authors and do not necessarily
advance over unconjugated polysaccharide vaccines, represent the official views of the National Institutes
with modest improvements in efficacy and durability, of Health, National Institute of Allergy and Infectious
although at an increased cost due to the complexities of Diseases.
polysaccharide conjugation chemistry. A further potential
advantage of protein conjugates is that they can benefit Conflict of interest
from an adjuvant to further increase their potency. In a
major step forward, PCMV technology was used to create Nikolai Petrovsky is an affiliate of Vaxine Pty Ltd which
the Typhax vaccine, a simpler and cheaper approach to has proprietary interests in Advax‑CpG adjuvant, while
polysaccharide conjugation whereby the polysaccharide is Kevin P. Killeen is an affiliate of Matrivax Inc. which has
trapped in a protein matrix rather than directly conjugated proprietary interests in the Typhax vaccine.
to the carrier protein. This achieves all the benefits of Author contributions
a polysaccharide-conjugate vaccine without involving
complex procedures and high costs. To further build on Conceptualization: All authors
this platform, we were able to show that the PCMV‑based Writing–original draft: Nikolai Petrovsky
Typhax vaccine can be conveniently combined with Advax- Writing–review & editing: All authors
CpG adjuvant, thereby delivering a typhoid vaccine of
st
unmatched potency, which for the 1 time has the potential Ethics approval and consent to participate
to provide long-term durable protection against S. Typhi Not applicable.
without the need for regular boosters. This could further
raise the bar for typhoid vaccine efficacy and durability. Consent for publication
An Advax‑CpG adjuvanted Typhax vaccine could make Not applicable.
typhoid vaccines more accessible for poor endemic
countries such as Nepal by reducing manufacturing costs Availability of data
and reducing the need for regular booster doses. This Further information on adjuvants developed as part of this
might thereby help bring the world one-step closer to program is listed on the NIH Adjuvant Database at https://
typhoid eradication. While Typhax PCMV antigen and vac.niaid.nih.gov/.
Advax‑CpG55.2 adjuvant have separately been shown
to be safe and effective in human testing, what is now References
needed is a human trial of the combination of these two
complementary technologies, with the potential to deliver 1. Khan MI, Soofi SB, Ochiai RL, et al. Epidemiology, clinical
presentation, and patterns of drug resistance of Salmonella
a typhoid vaccine of unmatched safety, efficacy, and Typhi in Karachi, Pakistan. J Infect Dev Ctries. 2012;6:704-14.
durability.
doi: 10.3855/jidc.1967
8. Conclusion 2. Typhoid GBD, Paratyphoid C. The global burden of typhoid
Advax‑CpG55.2‑adjuvanted Typhax induced high and and paratyphoid fevers: A systematic analysis for the
sustained serum bactericidal activity against S. Typhi Global Burden of Disease Study 2017. Lancet Infect Dis.
2019;19:369-381.
in mice, rabbits and non-human primates. It is thereby
a highly promising vaccine development candidate to doi: 10.1016/S1473-3099(18)30685-6
provide robust and durable protection against typhoid 3. Mohsen Y, Tarchichi N, Barakat R, et al. The different types
fever. of metallophores produced by Salmonella enterica: A review.

Volume 2 Issue 1 (2025) 97 doi: 10.36922/mi.4497