Human Vaccines & Immunotherapeutics: news

Enhanced-potency influenza vaccines are more immunogenic than standard vaccines in the elderly

Improved immune responses in the elderly were reported for three enhanced-potency influenza vaccines.¹ Adult residents of Hong Kong aged 65–82 years were randomized to receive, one of three newer vaccines designed for the elderly: a high-dose 3-valent vaccine, MF59-adjuvanted three-valent vaccine, and high-dose four-valent recombinant hemagglutinin vaccine, or a standard four-valent vaccine as comparator control.

All three enhanced-potency vaccines elicited comparable antibody and cellular responses that were higher than the comparator vaccine. The recombinant variant showed a superior response to the A(H3N2) vaccine strain that matched the virus in circulation at that time.

The elderly account for the majority of hospitalizations and deaths due to influenza infection. Due to a weakened immune system, the effectiveness of vaccination is lower in this age group, hence the need for enhanced-potency vaccines.

Mosunetuzumab brings clinical benefits to lymphoma patients

The bispecific MAb mosunetuzumab induced remission in almost half of B-cell lymphoma patients who relapsed after prior treatment. According to the results from a multi-center trial involving almost 200 evaluable subjects, 17% of aggressive cancer cases showed partial response and 18% complete response. The numbers were 19% and 43% in patients with the slow-growing disease.

Mosunetuzumab targets the CD20 antigen on B cells as well as the CD3ε peptide to engage T cells.

The standard of care for B-cell lymphoma is chemotherapy followed by CAR-T cell immunotherapy. “There is still a large need for new treatments in relapsed or refractory cases, since some patients fail CAR T and others are too sick to wait for cell manufacturing,” lead author Stephen Schuster of the University of Pennsylvania said. “One of the benefits of this treatment is that it’s ‘off-the-shelf,’ meaning it does not need to be manufactured for each patient.”

Among subjects with the refractory disease after CAR-T therapy, the recombinant cells increased after mosunetuzumab treatment.

Single-dose of vaccine may be sufficient to prevent HPV infection

Protection from the four HPV vaccine strains is comparable after one, two and three doses, according to a cross-sectional study involving 1,600 U.S women in the period 2009–16.² While unvaccinated subjects showed a 12.5% prevalence of HPV infection, the numbers were 2.4%, 5.1% and 3.1% in women who had been vaccinated with one, two, and three doses, respectively.

Vaccination is the most effective ways of preventing HPV-induced cancers; however, only half of U.S. adolescents complete the recommended series.

“HPV vaccine coverage is less than 10% globally because of poor vaccine uptake rates in many resource-limited countries. Ensuring boys and girls receive their first dose is a big challenge in several countries and a majority of adolescents are not able to complete the recommended series due to a lack of intensive infrastructure needed to administer two or three doses. [A] single-dose strategy could be substantial for reducing the burden of these cancers globally,” senior author Ashish Deshmukh of the University of Texas said.

It should be noted that long-term immunogenicity needs to be followed to see whether one-dose immunization provides for comparable persistence of antibody to two- or three-dose immunization.

Alzheimer’s disease vaccines promising after a preclinical trial

A combination vaccine approach elicited beta amyloid- and tau-specific antibodies and reduced brain levels of tau and amyloid plaques in a mouse model of Alzheimer’s disease (AD).³ The antibodies recognized pathological plaques in brain sections from AD patients. The two Advax^CpG-adjuvanted, MultiTEP platform-based vaccines, AV-1959R and AV-1980R, target the beta-amyloid protein and misfolded tau, respectively.

Another immunotherapeutic approach to AD, the tau-specific MAb gosuranemab (Biogen), failed in a mid-stage trial to show efficacy in treating the related neurodegenerative disease, progressive supranuclear palsy. Thus, the clinical development of gosuranemab in this condition was abandoned, but its development will continue for treating AD.

Progress on the Ebola vaccine front

The Ebola vaccine rVSV-ZEBOV (Merck) was approved by the U.S. Food and Drug Administration. The vaccine has been administered to nearly 300,000 people in the ongoing outbreak in the Democratic Republic of the Congo, which claimed >2,200 lives. Following the decision and earlier approval by European authorities, the international vaccine alliance Gavi initiated a global stockpile, which will make rVSV-ZEBOV available for free to low- and middle-income countries, and should be used for targeted vaccinations of at-risk populations.

Another Ebola vaccine, Ad26.ZEBOV/MVA-BN (J&J), is being deployed in neighboring Rwanda as a preventive measure to stop the spread of the outbreak. It will be administered to people aged ≥2 years in the regions bordering Congo.

Peanut allergy vaccine shows promise in a preclinical trial

An experimental peanut allergy vaccine successfully reprogrammed immune responses in mice. The vaccine is based on a peanut peptide packaged in a replication-deficient vaccinia virus. It is designed to shift the allergen-specific immune response from the harmful Th2 to the benign Th1 response.

“Already, the vaccine is showing signs of success, shifting peanut-specific immune responses in mouse models of peanut allergy, and in preliminary in vitro vaccination-like studies using human blood samples from clinically-confirmed peanut allergic people,” project leader Preethi Eldi of the University of South Australia said.

New typhoid vaccine fr children effective in a late-stage trial

A vaccine against Salmonella typhi prevented 80% of typhoid fever cases after 1 year in a Phase 3 study, which enrolled 10,000 children aged 9 months to 16 years in disease-endemic Nepal.⁴ The participants were randomized to receive the investigational vaccine, consisting of the Vi polysaccharide conjugated to a tetanus toxoid protein, or a meningococcal vaccine as control. The trial is ongoing to determine long-term immunity.

Typhoid fever is a major public health concern in developing countries, especially due to growing antibiotic resistance. “The burden of typhoid is so huge, we’re seeing families taking children into the hospital to be treated and being plunged into poverty paying for the costs of investigation and treatment with antibiotics,” senior author Andrew Pollard of University of Oxford told BBC News.

The vaccine, which was pre-qualified by the World Health Organization, is the first one designed for the most vulnerable group, which is children under 2 years old.

Almost 3% of Samoan population infected in a measles outbreak

The Pacific island state of Samoa has ended its state of emergency due to the measles outbreak, which has affected 5,600 and killed 81, mostly young children. The rate of disease spread has decreased, and government officials lifted emergency orders, such as closing schools and restricting travel.

Vaccine skepticism is blamed for the current outbreak, but a campaign in Samoa restored the uptake of the measles vaccine to 95%.

Zika vaccine improved fetal outcomes in a preclinical model

The DNA vaccine against Zika virus VRC5283 prevented fetal loss in pregnant macaques.⁵ The vaccinated animals showed reduced viremia, fetal infection, and placental damage compared to unvaccinated controls in a challenge study.

The mosquito-borne Zika virus, which surfaced in the Americas in 2015, causes serious birth defects and microcephaly in babies born to mothers infected during pregnancy. No vaccine is available for this disease.