Former Soviet-bloc countries and Europe among most vaccine-skeptical regions
One-third of people in France disagree that vaccines are safe, which is the highest percentage of any polled country. According to the Wellcome Global Monitor 2018,Citation1 which surveyed 140,000 people in 140 countries, people in Europe and former Soviet republics are least likely to trust vaccines with just 40% in Eastern Europe holding such trust. Conversely, the highest level of confidence in vaccines was reported in South Asia (95%) and Eastern Africa (92%).
Globally, 7% of people disagree that vaccines are safe, and 6% of parents said their children had not received any vaccine. Trust in vaccines was positively correlated with general trust in scientists.
The World Health Organization (WHO) has identified vaccine hesitancy as one of the world’s top 10 public health threats.
First immunotherapy successful in delaying type 1 diabetes
The anti-CD3 MAb teplizumab (Provention Bio) reduced the rate of type 1 diabetes (T1D) in high-risk people.Citation2 The Phase 2 trial enrolled 55 children and 21 adults with a family history of the disease and high-level blood markers, which practically ensure T1D diagnosis during their lives. A single two-week course of treatment decreased the rate of T1D onset during the following year from 36% in the placebo group to 15% in the experimental group. The median time to diagnosis was delayed by 2 y.
“This is the first trial to successfully delay the diagnosis of T1D in at-risk individuals,” said study chair Kevan Herold of Yale University. “It is all the more remarkable that a single 14-day course of this drug was able to significantly reduce the number of patients who have been diagnosed even six years into the trial.”
Adjuvanted influenza vaccine protected 60% of older adults
The effectiveness of influenza vaccination in the UK last season was 44% according to Public Health England. Notably, the adjuvanted vaccine prevented 62% of doctor visits in people aged ≥65 y, compared to 50% for all vaccine types.
“It’s also really promising to see that this year around 3 million children were vaccinated – and we’re expanding and improving the vaccine program so that from next year it will be available to all children in primary school,” British Public Health Minister Seema Kennedy said.
Durvalumab had promising late-stage data in small-cell lung cancer
The anti-PD-L1 MAb durvalumab (Imfinzi, AstraZeneca) in combination with chemotherapy has brought a survival benefit for patients with newly diagnosed extensive-stage small-cell lung cancer (SCLC) compared to chemotherapy alone. Specific results of the Phase 3 Caspian trial have not been announced apart from a statement that they were significant and clinically meaningful.
Durvalumab can be combined with more chemotherapy drugs than the only PD-L1 inhibitor approved for the treatment of SCLC, atezolizumab (Tecentriq, Roche). Durvalumab has so far been approved for unresectable, stage III non-SCLC.
Updated recommendation from the US CDC on HPV and other vaccines
HPV vaccine is recommended for all US men up to 26 y of age, increased from the previous 21 y. The decision by the US Centers for Diseases Control and Prevention (CDC)’s Advisory Committee on Immunization Practices (ACIP) follows a large meta-analysis suggesting the vaccine reduces the incidence of genital warts in men.Citation3 HPV is responsible for 90% of anal cancer, 70% of oral, throat and neck cancers, and 60% of penile cancer cases. ACIP has also recommended that adults up to 45 y of age discuss with their physicians about being vaccinated.
ACIP has further downgraded the recommendation for routine use of the 13-valent pneumococcal conjugate vaccine in older adults, stating it is no longer necessary for all healthy people aged ≥65 y to receive the vaccine.
In addition, ACIP has recommended that people with high risk of contracting group B meningococcal disease receive booster doses of the MenB vaccine, and that all children who missed hepatitis A vaccine get one up to the age of 18.
Pembrolizumab therapy sees benefits in multiple cancer types
The PD-1 inhibitor pembrolizumab (Keytruda, Merck) combined with chemotherapy-extended survival by one third in patients with recurrent head-and-neck cancer and high levels of PD-L1 compared to chemotherapy alone. Three-year survival rate was 33% in the experimental group and 8% in the control group. Smaller benefit was observed for subjects with low PD-L1 levels and for pembrolizumab monotherapy.
The checkpoint-blocking MAb along with two chemotherapeutics targeting the BRAF mutation in melanoma also extended progression-free survival by more than a half in patients with metastatic, BRAF-positive melanoma, compared to subjects receiving chemotherapy alone.Citation4 However, the Phase 2 study reported the effect was not statistically significant. The immunotherapeutic group also saw more than twice the rate of adverse events.
In another Phase 3 trial, pembrolizumab showed a 39% survival rate at 2 y compared to 22% after chemotherapy in patients with HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma who had high levels of the PD-L1 marker. In subjects with low PD-L1 levels, immunotherapy was as efficacious as chemotherapy. Combining the two treatments brought no additional benefits.
Finally, pembrolizumab showed a 5-y survival of 25% as a first-line therapy of advanced NSCLC, compared to 15% in subjects who had received prior chemotherapy. The figure had been 5% before immunotherapy became available.
All results were presented at the American Society of Clinical Oncology Annual Meeting.
Dengvaxia approved for children in US territories
The US Food and Drug Administration (FDA) has approved the dengue vaccine Dengvaxia for people aged 9–16 y living in dengue-endemic regions who have been infected by the virus. This means the approval is limited to Puerto Rico, the US Virgin Islands, American Samoa and Guam. Unlike European authorities, which approved Dengvaxia for people up to 45 y old, the FDA has decided on a younger cohort based on large clinical trials indicating that the vaccine is 76% effective in subjects in this age group.
Dengvaxia has been a subject of a major scandal in the Philippines national campaign, when it was launched before it was determined that the vaccine exacerbates the course of infection in dengue-naïve subjects.
New vaccine against meningitis B was immunogenic in a preclinical model
A new native outer membrane vesicle vaccine against group B meningococci elicited higher protective antibody responses against more bacterial strains than a licensed vaccine in infant rhesus macaques.Citation5 The two vaccines currently in use contain the same active component, the Factor H-binding protein, but are ineffective against some group B strains and cannot be used in children under 10 y due to low immunogenicity.
“This shows that the vaccine has the potential to be developed into a more broadly protective vaccine for humans, to extend coverage to infants and toddlers, which are the age groups among the highest risk of developing meningococcal disease, and to increase vaccine safety,” lead author Peter T. Beernink of University of California, San Francisco said.
Shingrix has been approved in China
Chinese authorities have approved the shingles vaccine Shingrix (GSK) for use in people aged ≥50 y. The decision is based only on foreign trial data, and the manufacturer is required to conduct post-approval studies in China, investigating especially Shingrix adjuvant, an extract from soapbark tree, which might increase the risk of immune disorders.
Shingles, which is a serious sequela of long-term latent infection by the varicella zoster virus, causes a painful rash in ~3 million Chinese adults annually.
WHO expands vaccination campaign amid second largest Ebola outbreak in history
The Ebola outbreak in the Democratic Republic of the Congo has claimed more than 1500 lives since August 2018. Health-care workers have administered >130,000 doses of the rVSV-ZEBOV-GP vaccine (Merck) in the so-called ring-vaccination approach, in which contacts of people who contracted Ebola, and their contacts, are offered the vaccine.
WHO panel of experts now recommended that vaccination is expanded to entire villages and neighborhoods where cases have been reported. The addition of a second vaccine, the investigational Ad26.ZEBOV/MVA-BN (J&J), is also being debated.
Northern-hemisphere seasonal influenza vaccine was 30% effective last season
Influenza vaccination in the 2018/9 season was ~30% effective against the disease and prevented 40–90 thousand hospitalizations, according to the CDC. The season saw two waves of infection caused by different influenza strains. The vaccine was 44% effective against the first wave caused by the A(H1N1)pdm09 strain, while due to a mismatch in the vaccine strain it was not effective against the second wave caused by the H3N2 virus.
References
- Wellcome Global Monitor 2018.( published 2019 June 19); [accessed 2019 July 2]. https://wellcome.ac.uk/reports/wellcome-global-monitor/2018
- Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, et al. Type diabetes trialnet study group. An Anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med. 2019. doi:10.1056/NEJMoa1902226.
- Drolet M, É B, Pérez N, Brisson M. HPV vaccination impact study group. Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis. Lancet. 2019. doi:10.1016/S0140-6736(19)30298-3.
- Ascierto PA, Ferrucci PF, Fisher R, Del Vecchio M, Atkinson V, Schmidt H, Schachter J, Queirolo P, Long GV, Di Giacomo AM, et al. Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma. Nat Med. 2019;25(6):941–46. doi:10.1038/s41591-019-0448-9.
- Beernink PT, Vianzon V, Lewis LA, Moe GR, Granoff DM. A meningococcal outer membrane vesicle vaccine with overexpressed mutant FHbp elicits higher protective antibody responses in infant rhesus macaques than a licensed serogroup B vaccine. MBio. 2019;10:3. doi:10.1128/mBio.00669-19.