Covid-19 vaccine has demonstrated high effectiveness in field use
Israel has reported only 20 infections among 130,000 people who received both doses of the mRNA vaccine for SARS-CoV-2 (Pfizer & BioNTech), which corresponds to an effectiveness rate of 92%. According to preliminary results of the surveillance study, all 20 patients had mild illness without the need of hospitalization. Israel is on the forefront of the global vaccine campaign with >40% of its population having completed the regimen.
Other vaccines are being developed and deployed. The EU has approved another mRNA vaccine (Moderna) for use in adults (already in use in the US, Canada and Israel), as well as the adenovirus-vectored vaccine ChAdOx1-S (AstraZeneca; marketed in the U.K, India and Argentina). Additionally, the adenovirus-based candidate Ad26.COV2.S (J&J) was 66% effective in a trial with 44,000 volunteers.
Antibodies for passive immunization have also proven effective. Following the US approval of bamlanivimab (LY-CoV555, Eli Lilly), another antibody (ADG-2, Adimab) engineered from natural antibodies following a 2003 infection with the related SARS coronavirus disabled replication and prevented disease in a mouse model.Citation1 In addition, a cocktail of two antibodies, REGEN-COV (Regeneron) prevented symptomatic disease in all trial participants (˜190) who lived in the household with someone who contracted the disease.
Epidemiologists have reported emerging strains that might be less vulnerable to vaccine-induced antibodies. The variant 501Y.V2 identified in South Africa has several mutations in the spike protein, which is the primary vaccine target. It was much less amenable to neutralization by patient sera than previous variants,Citation2,Citation3 and vaccination induced protection in fewer than half of subjects in a trial testing the nanoparticle protein vaccine NVX CoV2373 (Novavax), compared to ˜85% for other strains. However, 501Y.V2, which now accounts for 90% of Covid-19 cases in South Africa, had a smaller effect on the neutralizing potency of antibodies isolated from subjects immunized with one of the mRNA vaccines.Citation4
In an attempt to increase coverage, some countries are experimenting with dosage levels and timing, which some fear might accelerate further emergence of new variants of SARS-CoV-2.
Although pharma companies collaborate to scale up production of the licensed vaccines, shortage of doses has already led to some political conflict. Equitable distribution of vaccines all over the world is the aim of a collaboration of countries and organizations called COVAX, which plans if possible to distribute 2 billion doses by the end of 2021.
Checkpoint inhibition immunotherapy improves survival of mesothelioma patients
The anti-PD-1 antibody nivolumab (Opdivo, BMS) extended median survival by 2.6 months compared to placebo (9.2 versus 6.6 months) in the randomized Phase 3 CONFIRM trial involving 330 subjects with relapsed pleural or peritoneal mesothelioma. The experimental cohort also reported 39% lower risk of disease progression or death. PD-L1 levels were not predictive of outcome. This is the first late-stage trial demonstrating benefit of an investigational treatment for mesothelioma
Therapeutic HPV vaccine reduced the incidence of precancerous lesions in a Phase 2 trial
>60% of women with HPV-associated vulvar dysplasia saw at least a one-quarter reduction of lesions following treatment with the investigational vaccine VGX-3100 (Inovio), which targets HPV strains 16 and 18. Three of 20 trial participants reported complete remission with no detectable virus. The vaccine was safe, with no discontinuations due to adverse events. Vulvar dysplasia is a precancerous disease with no treatment options other than surgical removal. It is induced by HPV infection. VGX-3100 targets the E6 and E7 viral antigens that play a crucial role in transformation.
Phase 1 started for a personalized cancer immunotherapy
First patients with HPV-negative head-and-neck cancer were treated with the experimental neoantigen vaccine TG4050 (Transgene). The myvac technology is based on sequencing the tumor, selecting the most suitable neoantigens using artificial intelligence, and delivering corresponding DNA in an MVA viral vector. TG4050 can target up to 30 patient-specific neoantigens. The protocol is initiated after surgery and concomitantly with adjuvant therapy. Half of participants in the Phase 1 trial will receive the vaccine immediately following standard-of-care treatment, while the other half only after disease recurrence.
A parallel study is investigating TG4050 in ovarian cancer.
Autologous natural killer cell therapy potentiates immune checkpoint blockade
Natural killer (NK) cells isolated and expanded from patients’ own tumors can remodel the tumor microenvironment to make it more susceptible to checkpoint inhibitors. Using lung cancer cells and a mouse xenograft model, researchers showed that lung cancer from non-responding patients can be sensitized to PD-1 blockade (nivolumab) by autologous NK cells, expanded and primed ex vivo.Citation5 Furthermore, the NK cells induced interferon-γ signaling to rescue killing by exhausted tumor-infiltrating lymphocytes.
“We needed to find a one-two punch to dismantle the hostile lung tumor environment,” senior author Ali Ashkar of McMaster University said. “Not only is this providing a new treatment for hard-to-treat lung cancer tumors with the natural killer cells, but that treatment also converts the patients who are not responsive to PD1-blockade therapy into highly responsive candidates for this effective treatment.”
PCV-15 under priority review in the US
The US Food and Drug Administration has granted priority review for the 15-valent pneumococcal conjugate vaccine V114 (Merck). The decision is based on trial data showing that V114 was non-inferior to the marketed PCV-13 Prevnar 13 for the strains included in both vaccines, and offered higher protection against the two additional strains in older adults.
V114 is designed to prevent invasive pneumococcal disease in adults, and a related vaccine is being developed for pediatric population.
Multiple sclerosis vaccine induces tolerance in mice
A nanoparticle mRNA vaccine delayed onset and reduced the severity of disease in a preclinical model of multiple sclerosis.Citation6 The delivery of autoantigen induced presentation by splenic cells without the expression of costimulatory signals, leading to reduced effector T cells and increased levels of specific Tregs without suppression of immune response to unrelated targets.
References
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