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Central Research

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Challenges in clinical research of vaccines for emerging and re-emerging diseases

The SARS-CoV-2/COVID-19 pandemic marked a milestone in the accelerated development and testing of vaccines against this disease. In the desire to control the damage derived from it, multiple candidates were developed and tested by different public and private entities, or by an association between them, in various countries, resorting to emergency assessments of the safety and efficacy properties (even if preliminary) of these biologicals.

Thanks to these efforts, it was possible to reduce the rate and number of people who unfortunately die because of COVID-19 and its complications. With this, various complications also became evident at a global level, including:

• Access to new vaccines was not equitable for all countries.

• Clinical trials tended to be concentrated in a few sites, which could have had an impact

on having little information on safety and efficacy in genetically distinct or heterogeneous groups.

• Vaccine manufacturing capacity was overwhelmed by the generated global demand.

• Investment in new vaccine research continues to present an imbalance, with few countries leading and multiple without development or own tests.

Given these circumstances, it also became evident • the need to pay greater attention to various emerging and re-emerging diseases and to consider the effects that multiple comorbidities may have on them (overweight, obesity, diabetes, malnutrition, among others).

To cite an example, tuberculosis (TB) remains the first historical cause of death caused by a single infectious agent worldwide since, in 2019, TB caused 1.4 million deaths and 10 million new cases.

For this disease, a recent meta-analysis reported that patients with diabetes have a two- to five-fold higher risk of developing TB than patients without TB. Also, it is estimated that 16% of newly diagnosed TB cases occur with diabetes, and it is estimated that 4.1% of patients with diabetes will eventually develop TB.

Additionally, it is estimated that in 2021 there were 537 million people affected worldwide with diabetes, with a projection of 643 million by 2030 and up to 783 million cases by 2045. In that sense, in the case of comorbidity with TB, diabetes favors more severe clinical manifestations of TB than those in patients without this condition, including widespread lung damage, especially in chronic comorbidity.

Despite the above, the evaluation of new treatments, diagnostic methods, or preventive measures against TB in the context of diabetes still constitutes an area little explored, both internationally and nationally, without information available today on the efficacy of the protection of any new TB vaccine candidate in the context of diabetes, at the level of clinical studies. A recent trial on the new vaccine candidate, VPM1002, excluded people with diabetes in a Phase 2 safety and immunogenicity clinical study. The TB-diabetes duo is not the only one that deserves greater attention to reduce its catastrophic consequences. We still have lags concerning dengue, Zika, Chikungunya, and cancer, to name just a few more examples.

In that sense, it can be thought that some relevant points and challenges in the clinical research of vaccines for emerging and re-emerging diseases could be:

1. Increase awareness of the need to invest in national research and development to speed response and reduce dependence on third parties.

2. Increase and be accurate during epidemiological surveillance to define which infectious agent is spreading, how often, and quickly.

3. Facilitate the transfer of biological samples containing the pathogens of interest between hospitals and health centers with the institutions dedicated to research to speed up the analysis of sequences that result in better and faster solutions (vaccines).

4. To facilitate clinical studies on the safety and efficacy of such vaccines to be conducted in genetically distinct or heterogeneous groups.

5. Facilitate the regulatory analysis by the entities in charge of the pharmacovigilance of vaccine candidates so that the relevant clinical studies can be carried out quickly and discard or modify what is essential to have a safe and effective vaccine in less time.

6. Include, as soon as they pass the safety tests, people with different risk factors for infections (obesity, overweight, diabetes, malnutrition, among others) in clinical studies to verify the safety of new vaccines.

7. Favor the development of vaccines that are “friendly” with logistics, that is, give preference to those that can be transported at room temperature, refrigeration, freezing, and deep freezing, in descending order of priority.

8. Whenever this is not possible, improve supply and logistics chains to remote populations or where healthcare centers do not have deep-freezing equipment.

Undoubtedly, additional aspects must be considered, which must have the consensus and best practices of the areas involved.