The Vaccine Revolt of 1904, Rio de Janeiro, Brazil

A review of the literature on the Vaccine Revolt shows that it continues to be treated in an overly simplistic manner as a “structure” subjected to some form of regulation, from which its dynamics can be explained and its “root causes” identified. It is possible to forge a new, more cautious historiographical path, seeking to view this “structure” as a rhizome, as a loosely connected ensemble that exists under unstable circumstances whose precarious (dis)order cannot be grasped in its complexity by a reductionist analysis. Another historiographical approach that can shed new light on the popular revolt of 1904 situates it in the context of its links to the history of the smallpox vaccine and its diffusion. Viewing the episode as equally relevant to the history of science and technology, this article proposes to “vaccinate the Vaccine Revolt”—that is, to reintroduce the smallpox vaccine as a protagonist in the events—highlighting the need to treat the revolt as a chapter of a sociotechnical history; after all, what could be more sociotechnical than a technoscientific artifact that gave its name to a popular revolt? This is a history of scientists convinced of the superiority of their technical knowledge and of their right to exercise their power for the good of the public, who would be obliged to comply; most of all, it is a history without the problematic distinctions between content and context, between rationality and irrationality, between science and society. It is also a history of the popular mobilization on the streets of downtown Rio de Janeiro, exemplified by the vigorous resistance mounted in the working-class neighborhood of Saúde under the command of the Black man known as Prata Preta, which serves as a counterpoint to top-down historical narratives more concerned with the comings and goings of White political elites and coup-plotting, positivist-inspired generals, marked by the symptomatic exclusion of Black and working-class actors. It also serves to emphasize the symptomatic absence of the voice of Prata Preta, who was imprisoned and summarily banished without any due process. The fact that he was silenced has made it easier to construct allegories about “the people,” portraying them as heroic opponents of elite oppression or the exact opposite: an antiheroic, dangerous, and disposable rabble. Among the entourage of characters who have been silenced, one should also note the absence of women’s voices; although vaccine opponents rallied around the claim that they were defending against the “violation” of women’s bodies, nothing was heard from women’s mouths. Finally, revisiting the history of the Vaccine Revolt offers another opportunity to unmask the project of an authoritarian political, military, and scientific elite, with a particular focus on Oswaldo Cruz, one of Brazil’s greatest champions of science. In the name of science and public health, that elite envisioned a modern Brazil, while remaining ignorant of the daily nightmare lived by the vast majority of the Black, poor, and marginalized population.

Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and Stockpiling

Although smallpox has been eradicated globally, the potential use of the smallpox virus in bioterrorism indicates the importance of stockpiling smallpox vaccines. Considering the advantages of microneedle-based vaccination over conventional needle injections, in this study, we examined the feasibility of microneedle-based smallpox vaccination as an alternative approach for stockpiling smallpox vaccines. We prepared polylactic acid (PLA) microneedle array patches by micromolding and loaded a second-generation smallpox vaccine on the microneedle tips via dip coating. We evaluated the effect of excipients and drying conditions on vaccine stability in vitro and examined immune responses in female BALB/c mice by measuring neutralizing antibodies and interferon (IFN)-γ-secreting cells. Approximately 40% of the virus titer was reduced during the vaccine-coating process, with or without excipients. At −20 °C, the smallpox vaccine coated on the microneedles was stable up to 6 months. Compared to natural evaporation, vacuum drying was more efficient in improving the smallpox vaccine stability. Microneedle-based vaccination of the mice elicited neutralizing antibodies beginning 3 weeks after immunization; the levels were maintained for 12 weeks. It significantly increased IFN-γ-secreting cells 12 weeks after priming, indicating the induction of cellular immune responses. The smallpox-vaccine-coated microneedles could serve as an alternative delivery system for vaccination and stockpiling.

Epicutaneous immunization with modified vaccinia Ankara viral vectors generates superior T cell immunity against a respiratory viral challenge

Modified Vaccinia Ankara (MVA) was recently approved as a smallpox vaccine. Variola is transmitted by respiratory droplets and MVA immunization by skin scarification (s.s.) protected mice far more effectively against lethal respiratory challenge with vaccinia virus (VACV) than any other route of delivery, and at lower doses. Comparisons of s.s. with intradermal, subcutaneous, or intramuscular routes showed that MVAOVA s.s.-generated T cells were both more abundant and transcriptionally unique. MVAOVA s.s. produced greater numbers of lung Ova-specific CD8+ TRM and was superior in protecting mice against lethal VACVOVA respiratory challenge. Nearly as many lung TRM were generated with MVAOVA s.s. immunization compared to intra-tracheal immunization with MVAOVA and both routes vaccination protected mice against lethal pulmonary challenge with VACVOVA. Strikingly, MVAOVA s.s.-generated effector T cells exhibited overlapping gene transcriptional profiles to those generated via intra-tracheal immunization. Overall, our data suggest that heterologous MVA vectors immunized via s.s. are uniquely well-suited as vaccine vectors for respiratory pathogens, which may be relevant to COVID-19. In addition, MVA delivered via s.s. could represent a more effective dose-sparing smallpox vaccine.

Illustrating the Smallpox Vaccine in Hungary 1798-1850

This dissertation explores the images in the three treatises on the smallpox vaccine, which were illustrated between 1798 and 1850 in Hungary, which are János Stand’s, Sámuel Váradi’s and Mihály Kováts’s publications. It looks at the background of their authors and the production of their images, as well as the quality of the illustrations. As all three treatises have one illustration and they all follow the same visual strategy, the dissertation also seeks to describe and identify the scopes of such images, and to define their role in the implementation of the practice of vaccination in the wider public. Furthermore, the wider context of the images is also outlined, which aims at demonstrating what the illustrations can tell about contemporary medical culture and publishing in Hungary, the cultural dominance of Vienna within the Empire, and the transmission of knowledge, images, and cowpox matter in Europe and the Habsburg territories.

MVA Vector Vaccines Inhibit SARS CoV-2 Replication in Upper and Lower Respiratory Tracts of Transgenic Mice and Prevent Lethal Disease

Replication-restricted modified vaccinia virus Ankara (MVA) is a licensed smallpox vaccine and numerous clinical studies investigating recombinant MVAs (rMVAs) as vectors for prevention of other infectious diseases have been completed or are in progress. Two rMVA COVID-19 vaccine trials are at an initial stage, though no animal protection studies have been reported. Here, we characterize rMVAs expressing the S protein of CoV-2. Modifications of full length S individually or in combination included two proline substitutions, mutations of the furin recognition site and deletion of the endoplasmic retrieval signal. Another rMVA in which the receptor binding domain (RBD) flanked by the signal peptide and transmembrane domains of S was also constructed. Each modified S protein was displayed on the surface of rMVA-infected human cells and was recognized by anti-RBD antibody and by soluble hACE2 receptor. Intramuscular injection of mice with the rMVAs induced S-binding and pseudovirus-neutralizing antibodies. Boosting occurred following a second homologous rMVA but was higher with adjuvanted purified RBD protein. Weight loss and lethality following intranasal infection of transgenic hACE2 mice with CoV-2 was prevented by one or two immunizations with rMVAs or by passive transfer of serum from vaccinated mice. One or two rMVA vaccinations also prevented recovery of infectious CoV-2 from the lungs. A low amount of virus was detected in the nasal turbinates of only one of eight rMVA-vaccinated mice on day 2 and none later. Detection of subgenomic mRNA in turbinates on day 2 only indicated that replication was abortive in immunized animals.SignificanceVaccines are required to control COVID-19 during the pandemic and possibly afterwards. Recombinant nucleic acids, proteins and virus vectors that stimulate immune responses to the CoV-2 S protein have provided protection in experimental animal or human clinical trials, though questions remain regarding their ability to prevent spread and the duration of immunity. The present study focuses on replication-restricted modified vaccinia virus Ankara (MVA), which has been shown to be a safe, immunogenic and stable smallpox vaccine and a promising vaccine vector for other infectious diseases and cancer. In a transgenic mouse model, one or two injections of recombinant MVAs that express modified forms of S inhibited CoV-2 replication in the upper and lower respiratory tracts and prevented severe disease.