Human Vaccines & Immunotherapeutics: news

COVID-19 vaccines are deployed globally just one year after disease emergence

Several vaccines have received widespread regulatory approval and are being distributed in up to hundreds of millions of doses. Two nanoparticle mRNA vaccines lead the way with BNT162b1 (Pfizer & BioNTech) being administered in the U.S., Canada, Europe, Israel as well as a few Asian and Latin American countries, and mRNA-1273 (Moderna) in U.S. and Canada. Both vaccines showed >90% efficacy in Phase 3 clinical trials.

The adenovirus-vectored vaccine ChAdOx1-S (AstraZeneca) has been approved in U.K, India and Argentina. It showed mixed efficacy of 60-90% depending on dosage level. Several other vaccines with high reported efficacy rates are being deployed in the non-Western world, including adenovirus-based vaccine Sputnik V (Gamaleya, Russia) and inactivated virus vaccines (Sinovac & Sinopharm, China).

Other vaccines might soon join in. Large-scale trials are concluding for the adenovirus-based Ad26.COV2.S (J&J) and nanoparticle protein vaccine NVX-CoV2373 (Novavax).

All of these vaccines target the spike protein on the surface of SARS-CoV-2 and most are administered in two doses.

Public health authorities not only have to ensure the infrastructure for efficient and equitable delivery (some vaccines need to be deep-frozen until the point of application), but also address vaccine hesitancy. For example, a poll conducted in the U.S. has shown that only 60% of Americans are in favor of receiving a COVID-19 vaccine in the near future.

Cell-based and adjuvanted influenza vaccines show benefit in field use

The cell-based quadrivalent influenza vaccine (Seqirus) prevented more medical encounters due to influenza than the traditional egg-based vaccine. A series of studies investigated medical records of millions of U.S. individuals aged ≥4 years from the 2018-9 influenza season and found fewer relative hospitalizations and emergency-room visits in people vaccinated with the cell culture-produced vaccine.

In a parallel review of field studies, the MF59-adjuvanted trivalent influenza vaccine (Seqirus) showed higher efficacy than a non-adjuvanted quadrivalent vaccine and comparable efficacy to a high-dose trivalent vaccine formulation in subjects 65 years of age and older. The adjuvant is designed to enhance the levels and persistence of antibodies, which is especially important for the elderly age group with waning immunity.

Breast cancer vaccine set to start clinical trials

The U.S. Food and Drug Administration (FDA) has cleared a breast cancer vaccine (Anixa) to be tested in triple-negative breast cancer patients. The vaccine targets alpha-lactalbumin, which is expressed in mammary glands of lactating women and can be over-expressed in cancer.

The vaccine is designed to both treat and prevent breast cancer. While the trial will investigate effect on triple-negative tumors, other tumor types might be prevented as well.

PCV-20 received FDA’s priority review designation

The FDA has accepted priority review license application for the 20-valent pneumococcal conjugate vaccine 20vPnC (Pfizer) for adults. The decision is based on Phase 3 data showing that 20vPnC elicited non-inferior immune responses to the 13 shared strains of Streptococcus pneumoniae compared to the licensed Prevnar 13 (Pfizer) and six out seven additional strains contained in the 23-valent polysaccharide Pneumovax 23 (Merck) in subjects aged ≥65 years. 20vPnC is also being investigated under the breakthrough therapy designation in children.

Universal influenza vaccine candidate induces broad immunity in a Phase 1 trial

A chimeric influenza vaccine was safe and elicited broad and lasting antibody responses in a placebo-controlled Phase 1 trial involving 65 healthy subjects 18-39 years of age.¹ The regimen consists of two recombinant hemagglutinin vaccines consisting of a stalk domain from H1 influenza and variable head domains. The design favors generation of antibodies against the stalk, which is conserved across influenza strains unlike the hemagglutinin head.

The vaccine induced neutralizing stalk-specific antibodies that persisted for at least 18 months. Furthermore, transfer of serum from vaccinated subjects improved outcomes in an animal challenge experiment, suggesting potential protective effect.

Targeting the fas pathway might improve cancer immunotherapy outcomes

Inducing fas signaling improved CAR-T and bispecific antibody immunotherapy in animal cancer models.² By stimulating the pathway, T cells were able not only to kill the antigen-expressing cancer cells, but also other tumor cells that lacked the target antigen, the so-called ‘bystander killing’. Additionally, tumoral FAS expression predicted survival of B-cell lymphoma patients treated with CAR T-cell therapy in a clinical trial.

“This study should engender many clinical trials solving the common weakness of immunotherapies--antigen escape and relapse,’ senior author Joshua Brody of Icahn School of Medicine at Mount Sinai said. “Specifically, by combining immunotherapies with small molecule inhibitors that increase fas-signaling, which are already being used in the clinic, bystander tumor cell killing may be potentiated and eliminate antigen-loss variants from heterogenous tumors.”

Coxsackievirus B vaccine enters clinical trials

The placebo-controlled, double-blind, randomized Phase 1 PROVENT trial has started in healthy adult volunteers to evaluate safety of two dosage levels of the polyvalent coxsackievirus B virus vaccine PRV-101. The vaccine is administered in three injections four weeks apart.

Coxsackievirus B is an enterovirus that causes respiratory diseases and meningitis. It damages insulin-producing and gut-lining cells leading to type 1 diabetes or celiac disease. PRV-101 is designed to prevent autoimmunity associated with the virus.