IMU-201

A multicenter, randomized, open-label, phase II study (HERIZON; NCT02795988) was conducted to evaluate the clinical and immunologic efficacy of HER-Vaxx (IMU-131), a B-cell, peptide-based vaccine targeting HER2 overexpressed in 6% to 30% of gastroesophageal adenocarcinomas (GEA).

Patients (n = 36) with GEA were treated with standard-of-care chemotherapy (n = 17) or HER-Vaxx plus chemotherapy (n = 19), using the recommended phase 2 dose for the vaccine. Overall survival (OS; primary endpoint), safety, progression-free survival (PFS), clinical response (secondary endpoints), and vaccine-induced HER2-specific antibody levels in serum and correlation with tumor response rates (exploratory endpoints) were investigated.

A 40% OS benefit [HR, 0.60; median OS, 13.9 months; 80% confidence interval (CI), 7.52–14.32] for patients treated with HER-Vaxx plus chemotherapy compared with OS of 8.31 months (80% CI, 6.01–9.59) in patients that received chemotherapy alone. A 20% PFS difference was obtained for the vaccination arm (HR, 0.80; 80% CI, 0.47, 1.38). No additional toxicity due to HER-Vaxx was observed. The vaccine-induced high levels of HER2-specific total IgG and IgG1 antibodies (P < 0.001 vs. controls) that significantly correlated with tumor reduction (IgG, P = 0.001; IgG1, P = 0.016), had a significant capacity in inhibiting phosphorylation of the intracellular HER2-signaling pathways, mediated antibody-dependent cellular cytotoxicity, and decreased immunosuppressive FOXP3+ regulatory T cells.

HER-Vaxx plus standard chemotherapy exhibits an excellent safety profile and improves OS. Furthermore, vaccine-induced immune response was significantly associated with reduced tumor size compared with standard-of-care chemotherapy. The presented vaccination approach may substitute for treatment with trastuzumab, upon unavailability or toxicity, based on further evidence of equivalent treatment efficacy.

Despite Brazil's tradition of successful mass immunization programs, the country has been experiencing alarming declines in vaccination coverage, especially among children. That is aggravated by the growth of anti-vaccine movements and the spread of health misinformation in social media in the last decade, which have worsened during the COVID-19 outbreak. Several reports link populism and far-right politicians to anti-vaccination support worldwide, which was also the case in Brazil during president Jair Bolsonaro's administration. This project aimed to identify the circulating pro and anti-vaccine narratives in Portuguese on Twitter, during a crucial decision-making period regarding childhood vaccination in Brazil, from December 9, 2021, until February 9, 2022. From the over one million tweets and four million retweets collected, we identified two well-defined groups, one in favor and another against vaccination. Within the sample, we selected 1500 influencer tweets with the highest impact (>500 retweets) and conducted content analysis. Although the pro-vaccine influencers were more retweeted than anti-vaxxer ones, we observed that anti-vaccine movements were more succesful in framing discussions on Twitter. The subject of COVID-19 was the target of political polarization embedded in populist, anti-science and anti-traditional media discourses promoted by anti-vaxxers. As a counterpart, the pro-vaccine influencers reacted inarticulately, focusing on criticizing the anti-vaccination actors, attitudes, and policies instead of promoting vaccines. Based on reults, we claim that a well-coordinated network of health communicators from science centers and health institutions, in partnership with properly briefed social media influencers and fact-checking sources, would more efectively pre-tempt the public about vaccine misinformation.