Akshaya Santhanaraj

Introduction: Two subtypes of the Human Papilloma Virus, HPV-16 and HPV-18, account for 50% and 10% of all cervical cancer cases respectively¹. Preventative measures have been proven to be almost 100% effective against HPV-infiection². However, two challenges still exist regarding the current HPV vaccine: a lack of therapeutic value for individuals infected by the HPV virus and vaccine rejection^2-4. Studies have been conducted showing that combination therapies may provide therapeutic value for individuals infected with the HPV virus³. Studies have also been conducted showing that increasing knowledge related to vaccines does not significantly reduce long-term vaccine hesitancy⁴. Rather, the strength of key attitudes such as conspiratorial belief, disgust reactivity, and belief in an individualistic worldview impacts the extent of individual vaccine rejection⁵. These studies may provide insight on how to increase therapeutic value in current vaccination methods and reduce overall vaccine hesitancy^3-5.

 Challenge 1

Methods: A monotherapy and combination therapy against TC-1 carcinoma expressed HPV-16 E6 and E7 without PDL1 in a mouse model was employed. The combination therapy included PDS0101, bintrafusp alfa, and NHS-IL-12. Treatment began one week after implanting the TC-1 carcinoma with a control PBS vaccine, weekly injections of the liposomal R-DOTAP adjuvant, and weekly injections of the PDS0101 vaccine. Antitumor effects and immune cell types were analyzed in the spleen IFN-gamma ELIspot and flow cytometry. Results: In monotherapy, PDS0101 decreased tumor volume and tumor weights compared to the PBS control (p < 0.01). In combination therapy, there is greater control against tumor activity compared to PDS0101 alone. With the combination therapy, 13/16 mice had tumors smaller than 300 mm³.

 Challenge 2

Methods: 585 participants 60 years of age and older were provided 3 educational leaflets related to influenza and sepsis.⁴ After participants read the leaflets, demographic information was obtained and participants returned for a follow-up study 3 months later⁴. During the follow-up study, participants were asked if they received vaccinations for influenza and/or pneumococci⁴. The design assessed knowledge about primary and secondary health diseases, perceptions of risk, and vaccination intentions⁴. In another study, 323 participants in 24 different countries were surveyed about attitudes towards vaccinations⁵. Questions included beliefs in conspiracy theories, tolerance towards impingement of freedoms, attitudes toward blood and needles, and attitudes related to societal control over the individuall⁵. Results: Educational leaflets increased knowledge on the selected primary and secondary health diseases⁴. Immediate risk perceptions and intentions for vaccinations were also increased⁴. However, increased knowledge only has some impact on increased intentions for vaccination long-term⁴. Individuals who have a high belief in conspiracy theories had much stronger antivaccination attitudes, followed by individuals who had a low tolerance towards impingement on freedoms, individuals who had an aversion towards blood and needles, and individuals who believe society should have very little control over the individual⁵.

 Conclusions: Therapeutic vaccines are necessary to target viral antigens expressed by infected cells. A combination of different immunotherapeutic approaches, such as preventive prophylactic treatments as well as therapeutic treatments, can effectively eliminate HPV-associated tumors. Future research should focus on how increased knowledge impacts implementation intention to gain an understanding of the connection between long-term behaviors and new knowledge. Furthermore, by understanding the psychological factors behind vaccine hesitancy, there is a greater understanding of how the repetition of evidence-based information may not be productive in decreasing antivaccination sentiments. Rather, communication-based solutions should be of greater focus.

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3. Smalley Rumfield C, Pellom ST, Morillon II YM, Schlom J, Jochems C. Immunomodulation to enhance the efficacy of an HPV therapeutic vaccine. Journal for ImmunoTherapy of Cancer. 2020;8(1). doi:10.1136/jitc-2020-000612  https://jitc.bmj.com/content/8/1/e000612.long
4. Eitze, S., Heinemeier, D., Schmid-Küpke, N. K., &amp; Betsch, C. (2021). Decreasing vaccine hesitancy with extended health knowledge: Evidence from a longitudinal randomized controlled trial. Health Psychology, 40(2), 77–88. https://doi.org/10.1037/hea0001045
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