Human Vaccines & Immunotherapeutics: news

COVID-19 vaccines and immunotherapies progress through clinical trials

30,000 healthy adults are being enrolled for a double-blind, placebo-controlled Phase 3 study, which will determine the safety and protective efficacy of the RNA vaccine mRNA-1273 (Moderna). The vaccine, which is administered in two doses one month apart, was safe and immunogenic in a Phase 2 trial.¹

Another vaccine shown to be safe and immunogenic in adults in a randomized double-blind, placebo-controlled Phase 2 trial is an adenovirus type 5-vectored spike protein vaccine developed and tested in China.²

Another adenovirus-based candidate ChAdOx1 nCoV-19 (AstraZeneca), administered in two doses one month apart, showed good safety and immunogenicity profiles in ~1,000 healthy adults enrolled into a Phase 1/2 trial in the UK.³

Two more vaccines are ready for Phase 1 trials: Ad26-vectored DNA vaccine (J&J) are being examined in ~1,000 adults including a cohort of elderly subjects, and a nanoparticle RNA vaccine based on replicating Alphavirus repRNA-CoV2S was shown to induce neutralizing antibody and cellular immune responses in mice and non-human primates.⁴

Additionally, two immunotherapies are being trialed. The inhaled formulation of interferon-β SNG001 (Synairgen) decreased the risk of COVID-19 patients developing severe disease by 80% compared to placebo in a double-blind trial involving 100 subjects in UK hospitals.

A humanized MAb CPI-006 (Corvus) stimulating a variety of immune cells is being investigated in 30 COVID-19 patients. The MAb was tested successfully in subjects with other infectious diseases and cancer.

Licensed vaccines are extremely safe, study finds

Adverse events caused by the 57 vaccines approved by the U.S. Food and Drug Administration (FDA) in 1996-2015 were not life-threatening and of limited clinical significance. A comprehensive review found 58 safety-related label modifications for 25 of the studied brands.⁵ One vaccine, rotavirus vaccine RotaShield, was withdrawn due to increased risk for intussusception.

The study highlights the robustness of the approval process and post-marketing surveillance in the U.S., as adverse events were reported largely via the FDA’s Vaccine Adverse Event Reporting System.

Influenza vaccination decreases the risk of heart and Alzheimer’s diseases

Two studies show indirect benefits of influenza vaccination. In one, adults 50 years of age or older were 28%, 47% and 85% less likely to suffer heart attack, transient ischemic attack and cardiac arrest, respectively, during the year following vaccination. The risk of heart disease is increased by influenza infection due to imposed stress.

“[Older adults] should have the highest vaccination rates because they are the most at risk; however, our findings show the opposite – flu vaccinations are under-utilized,” lead author Roshni Mandania of Texas Tech said.

Another study found that influenza vaccination is associated with a 6% lower risk of Alzheimer’s disease in the elderly aged 75-84, and the earlier a subject gets the first dose, the greater the benefit. Even more pronounced association was reported for the pneumococcal vaccine, which correlated with up to 30% lower risk of Alzheimer’s dementia in 5,000 subjects 65-75 years old.

Engineered macrophage therapy for cancer enters clinical trial

Chimeric antigen receptor (CAR) macrophage treatment targeting the HER2 protein will be tested in an early trial in patients with recurrent or metastatic HER2-overexpressing solid tumors. CAR therapies, traditionally utilizing T cells, have been largely unsuccessful in solid tumors due to immunosuppressive tumor microenvironments and limited trafficking. CAR-M CT-0508 has been shown in preclinical trials to overcome these limitations and to elicit broad anti-tumor immune responses.

HPV vaccine sentiment is getting more negative on Facebook

45% of HPV vaccine-related posts on Facebook show negative tone with frequent focus on barriers to vaccination.⁶ According to the report, which studied 6,500 public posts between 2006 and 2016, sentiment has worsened overall despite the vaccine’s excellent safety record and ability to prevent HPV-related cancers.

“The representation of the HPV vaccine has not only worsened, but negative posts toward the HPV vaccine have received more public engagement, and evidence shows that these negative posts have generated momentum for other related negative posts,” the sole author Monique Luisi of University of Missouri said.

Investigational Lyme disease vaccine was immunogenic in a mid-stage trial

Lyme disease vaccine candidate VLA15 (Valneva) was immunogenic with no adverse events in a placebo-controlled Phase 2 study involving 570 healthy adults up to 65 years old. VLA15 targets six serotypes of Borrelia burgdorferi prevalent in the US and Europe. Three injections induced antibodies against all serotypes, including in the elderly.

The vaccine contains the bacterial Outer surface protein A, one of the most prominent surface antigens of Lyme borreliosis. It is alum-adjuvanted and administered intramuscularly.

Ebola vaccine was approved in the EU

The European Commission has approved a two-vaccine regimen for the prevention of Ebola in people aged ≥1 year. The regimen consists of two non-replicating viral vaccines that target the Zaire strain of Ebola: the adenovirus-vectored Ad26.ZEBOV (Zabdeno, J&J) followed eight weeks later by the Modified Vaccinia Ankara-vectored MVA-BN-Filo (Mvabea, Bavarian Nordic).

The vaccine was administered to 60,000 people in the recent Ebola epidemic in the Democratic Republic of the Congo. Field studies and clinical trials have shown that it is well tolerated and induces robust and durable immune responses.