Ethics of controlled human infection to study COVID-19

Development of an effective vaccine is the clearest path to controlling the coronavirus disease 2019 (COVID-19) pandemic. To accelerate vaccine development, some researchers are pursuing, and thousands of people have expressed interest in participating in, controlled human infection studies (CHIs) with severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) (1, 2). In CHIs, a small number of participants are deliberately exposed to a pathogen to study infection and gather preliminary efficacy data on experimental vaccines or treatments. We have been developing a comprehensive, state-of-the-art ethical framework for CHIs that emphasizes their social value as fundamental to justifying these studies. The ethics of CHIs in general are underexplored (3, 4), and ethical examinations of SARS-CoV-2 CHIs have largely focused on whether the risks are acceptable and participants could give valid informed consent (1). The high social value of such CHIs has generally been assumed. Based on our framework, we agree on the ethical conditions for conducting SARS-CoV-2 CHIs (see the table). We differ on whether the social value of such CHIs is sufficient to justify the risks at present, given uncertainty about both in a rapidly evolving situation; yet we see none of our disagreements as insurmountable. We provide ethical guidance for research sponsors, communities, participants, and the essential independent reviewers considering SARS-CoV-2 CHIs

Malaria vaccines getting close to clinical reality.

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Empowering malaria vaccination by drug administration.

Item does not contain fulltextAlthough significant progress has been made in clinical development, a protective malaria vaccine remains elusive. Here we review some of the immune subversive mechanisms used by the Plasmodium malaria parasite and propose a potentially effective strategy to achieve complete protection that may serve as a blue print for clinical usage. The premise is to modulate the immune response with drugs that neutralize suppressive functions and potentiate protective responses. Chloroquine may be a first attractive candidate facilitating protective cellular immune responses by improving cross-presentation and reducing suppressive regulatory T cell responses.1 juni 201

Human challenge trials in vaccine development, Rockville, MD, USA, September 28-30, 2017.

Item does not contain fulltextThe International Alliance for Biological Standardization organized the second workshop on human challenge trials (HCT) in Rockville, MD, in September 2017. The objective of this meeting was to examine the use of HCT, in response to the continuing human suffering caused by infectious diseases, preventable by the development of new and improved vaccines. For this, the approach of HCT could be valuable, as HCT can provide key safety, tolerability, immunogenicity, and efficacy data, and can be used to study host-pathogen biology. HCT can generate these data with speed, efficiency and minimal expense, albeit not with the same level of robustness as clinical trials. Incorporated wisely into a clinical development plan, HCT can support optimization or down-selection of new vaccine candidates, assuring that only the worthiest candidates progress to field testing. HCT may also provide pivotal efficacy data in support of licensure, particularly when field efficacy studies are not feasible. Many aspects of HCT were discussed by the participants, including new and existing models, standardization and ethics. A consensus was achieved that HCT, if ethically justified and performed with careful attention to safety and informed consent, should be pursued to promote and accelerate vaccine development.1 september 201

A consultation on the optimization of controlled human malaria infection by mosquito bite for evaluation of candidate malaria vaccines.

Early clinical investigations of candidate malaria vaccines and antimalarial medications increasingly employ an established model of controlled human malaria infection (CHMI). Study results are used to guide further clinical development of vaccines and antimalarial medications as CHMI results to date are generally predictive of efficacy in malaria-endemic areas. The urgency to rapidly develop an efficacious malaria vaccine has increased demand for efficacy studies that include CHMI and the need for comparability of study results among the different centres conducting CHMI. An initial meeting with the goal to optimize and standardise CHMI procedures was held in 2009 with follow-up meetings in March and June 2010 to harmonise methods used at different centres. The end result is a standardised document for the design and conduct of CHMI and a second document for the microscopy methods used to determine the patency endpoint. These documents will facilitate high accuracy and comparability of CHMI studies and will be revised commensurate with advances in the field

Report of a consultation on the optimization of clinical challenge trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, Bethesda, MD, USA.

Item does not contain fulltextDevelopment and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing pre-erythrocytic stage vaccines, some researchers believe that the sporozoite challenge model is less appropriate for testing blood stage vaccines. Here we report a consultation, co-sponsored by PATH MVI, USAID, EMVI and WHO, where scientists from all institutions globally that have conducted such clinical challenges in recent years and representatives from regulatory agencies and funding agencies met to discuss clinical malaria challenge models. Participants discussed strengthening and harmonizing the sporozoite challenge model and considered the pros and cons of further developing a blood stage challenge possibly better suited for evaluating the efficacy of blood stage vaccines. This report summarizes major findings and recommendations, including an update on the Plasmodium vivax clinical challenge model, the prospects for performing experimental challenge trials in malaria endemic countries and an update on clinical safety data. While the focus of the meeting was on the optimization of clinical challenge models for evaluation of blood stage candidate malaria vaccines, many of the considerations are relevant for the application of challenge trials to other purposes

A consultation on the optimization of controlled human malaria infection by mosquito bite for evaluation of candidate malaria vaccines.

Item does not contain fulltextEarly clinical investigations of candidate malaria vaccines and antimalarial medications increasingly employ an established model of controlled human malaria infection (CHMI). Study results are used to guide further clinical development of vaccines and antimalarial medications as CHMI results to date are generally predictive of efficacy in malaria-endemic areas. The urgency to rapidly develop an efficacious malaria vaccine has increased demand for efficacy studies that include CHMI and the need for comparability of study results among the different centres conducting CHMI. An initial meeting with the goal to optimize and standardise CHMI procedures was held in 2009 with follow-up meetings in March and June 2010 to harmonise methods used at different centres. The end result is a standardised document for the design and conduct of CHMI and a second document for the microscopy methods used to determine the patency endpoint. These documents will facilitate high accuracy and comparability of CHMI studies and will be revised commensurate with advances in the field