SARS-CoV-2 vaccines progress through clinical development
One of the most advanced COVID-19 vaccines in clinical development is the inactivated vaccine CoronaVac (Sinovac). 90% of 600 healthy volunteers who enrolled in a Phase 2 study developed neutralizing antibodies within two weeks of vaccination. A Phase 3 trial is upcoming in Brazil, one of the countries most affected by the pandemic.
Another inactivated vaccine (Sinopharm) was tested in three dosage levels and three schedules in a Phase 1/2 placebo-controlled trial. The mid-dose regimen induced neutralizing antibody responses in all subjects with no serious adverse events.
In a dose-finding, placebo-controlled Phase 1/2 trial with 45 participants, the mRNA vaccine BNT162b1 (Pfizer & BioNTech) elicited higher antibody levels than those measured in blood of people with prior SARS-CoV-2 infection. The majority of subjects in high-dose cohorts experienced mild fevers.
The U.S. National Institutes of Health is preparing three Phase 3 trials with the adenovirus-vectored candidate ChAdOx1 nCoV-19 (AstraZeneca), a nanoparticle-encapsulated mRNA vaccine (Moderna), and an Ad26-vectored DNA vaccine (J&J).
There are 21 COVID-19 vaccines in clinical development, according to the World Health Organization (WHO), also including an inactivated candidate developed by the Chinese Academy of Medical Sciences, which entered Phase 2 testing to determine optimal dose and immunogenicity in healthy people.
The SARS-CoV-2 sequence became available only ~6 months ago. Considering that before COVID-19 it was unheard of to get any new vaccine to a clinical trial in less than one year, it is astounding to see 21 vaccines in the clinic in only ~6 months.
FDA approves expanded indication for 9-valent HPV vaccine
The 9-valent recombinant HPV vaccine Gardasil-9 (Merck) is newly approved for prevention of oropharyngeal and other head-and-neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58. The decision by the U.S. Food and Drug Administration (FDA) is conditional upon Phase 4 verification studies. The vaccine had been approved for cervical, vulvar and vaginal cancers in women, and anal and head-and-neck tumors as well as genital warts in both sexes.
The broader scope of the vaccine’s prophylactic effect might improve coverage among U.S. teenagers, which has been only around 50%.
Pembrolizumab approved in the U.S. as first-line treatment of colorectal cancer
The FDA has approved the PD-1 inhibitor pembrolizumab (Keytruda, Merck) as the first option for patients with unresectable or metastatic microsatellite instability-high or mismatch repair-deficient colorectal cancer. This indication comprises ~5% of advanced colorectal cancer cases and has poor prognosis.
The decision is based on results in 300 patients suggesting that pembrolizumab doubled progression-free survival compared to chemotherapy to 17 months.
15-valent PCV succeeds in two late-stage trials
The 15-valent pneumococcal conjugate vaccine (PCV) V114 (Merck) was safe and immunogenic in two randomized, double-blind Phase 3 trials. In one, dubbed PNEU-WAY, 300 HIV-positive adults were randomized to receive V114 or PCV13 followed by the 23-valent polysaccharide vaccine Pneumovax 23 (Merck). Immune responses were comparable against the 13 common strains, and V114 also induced responses to the additional two serotypes.
The placebo-controlled PNEU-FLU study investigated concomitant or sequential administration of V114 and influenza vaccine in subjects aged ≥50 years. Both vaccines induced non-inferior immunogenicity when administered together.
The two trials were the first in 16 planned Phase 3 studies evaluating V114 in various populations.
Avelumab after chemotherapy improves outcomes in bladder cancer
The PD-L1 inhibitor avelumab (Bavencio, Merck & Pfizer) administered after standard-of-care chemotherapy extended median overall survival by ~50% compared to chemotherapy alone. The randomized Phase 3 “JAVELIN Bladder 100” study, which enrolled 700 patients with unresectable locally advanced or metastatic urothelial carcinoma, also showed an increased risk of adverse events following immunotherapy, particularly urinary tract infection, anemia and fatigue.
“It's practice-changing,” senior researcher Petros Grivas of Fred Hutchinson Cancer Research Center said. “Because instead of waiting until progression happens after the completion of front-line chemotherapy, with the new data, if there's no progression, we're going to hit it back to back with immunotherapy after the completion of chemotherapy.”
Ensilicated vaccines might improve the cold-chain problem
An ensilicated vaccine retained its immunogenicity after heat treatment or storage at room temperature for three years.Citation1 The technique uses silica coat to stabilize the tetanus toxoid protein in the diphtheria-tetanus-pertussis vaccine. The vaccine was immunogenic in mice after the vials were shipped within the UK by ordinary post and after heating to 100°C.
“Next, we will be working on developing a thermally-stable vaccine for diphtheria, and then pertussis. Eventually we want to create a silica cage for the whole DTP trivalent vaccine, so that every child in the world can be given DTP without having to rely on cold chain distribution,” senior author Asel Sartbaeva of University of Bath said.
Normally, vaccines need to be refrigerated all the way to their final destinations, which creates logistical problems for remote areas and developing countries.
Chikungunya vaccine was safe and immunogenic in early trial
The chikungunya vaccine candidate VLA1553 (Valneva) elicited virus-specific antibodies in all 120 healthy adults enrolled in a randomized, dose-finding Phase 1 study.Citation2 The immunity lasted for at least one year in all dose cohorts.
VLA1553 is a monovalent, single dose, live-attenuated vaccine under FDA’s fast-track designation. There is no licensed vaccine against the tropical, mosquito-borne chikungunya virus, which causes fevers, headaches and joint and muscle pain.
The Ebola epidemic in Congo has ended
Local authorities and WHO have announced the latest Ebola epidemic in the Democratic Republic of the Congo’s east has come to an end. It infected 3,500 people claiming 2,000 lives. It was considered one of the biggest public health challenges, because the affected region is torn with civil war. There were numerous attacks on healthcare workers, 11 of whom died.
The investigational Ebola vaccine rVSV-ZEBOV (Merck) has been successfully administered to 300,000 people, and shown to be effective in the so-called ring vaccination approach, in which contacts of infected people were tracked and vaccinated.
The deadliest Ebola epidemic, which ravaged West Africa in 2014-6, caused 30,000 cases and 11,000 deaths.
References
- Doekhie A, Dattani R, Chen YC, Yang Y, Smith A, Silve AP, Koumanov F, Wells SA, Edler KJ, Marchbank KJ, Elsen JMHVD, Sartbaeva A. Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization. Sci Rep 2020; 10(1):9243.
- Wressnigg N, Hochreiter R, Zoihsl O, Fritzer A, Bézay N, Klingler A, Lingnau K, Schneider M, Lundberg U, Meinke A, Larcher-Senn J, Čorbic-Ramljak I, Eder-Lingelbach S, Dubischar K, Bender W. Single-shot live-attenuated chikungunya vaccine in healthy adults: a phase 1, randomised controlled trial. Lancet Infect Dis 2020; S1473-3099(20)30238-3.