SARS-CoV-2 vaccines are tested in children
The mRNA vaccine BNT162b2 (BioNTech/Pfizer) is 91% efficacious in preventing symptomatic COVID-19 at least 6 months after vaccination. The trial, which included 12,000 people, identified 77 and 850 cases in the experimental and placebo groups, respectively. There were zero cases of severe disease following vaccination compared to 32 cases in the placebo cohort. The vaccine also protects against emerging variants; in South Africa, where the dangerous strain B.1.351 dominates, nine cases (six with B.1.351) were reported in 800 participants – all in the placebo arm. The vaccine is indicated for people 16 years and older. A Phase 3 trial in adolescents aged 12–15 years showed robust antibody responses and 100% efficacy; all 18 cases of COVID-19 were observed in the placebo group. A dose-escalation trial will test the vaccine in children 6 months to 11 years of age; if it shows acceptable safety, infants less than 6 months old will be enrolled.
Another mRNA vaccine, mRNA-1273 (Moderna), induces antibodies that persist for at least 6 months, as reported in a trial following up on 33 people; immune persistence was lower in older participants.Citation1 A trial with 12-to-17-year-olds is well underway, and an additional trial is enrolling almost 7,000 children aged 6 months to 11 years.
Both mRNA vaccines induced high antibody levels in pregnant women, and these antibodies were passed on to children through breast milk.Citation2,Citation3
The third vaccine investigated for efficacy in younger populations is the non-replicating adenovirus-based vaccine Ad26.COV2.S (J&J). A Phase 2 trial, which tests 1- and 2-dose regimens in adults, started enrolling adolescents 12 through 17 years old.
Other vaccines in clinical development include the inactivated, adjuvanted vaccine VLA2001 (Valneva), which was safe and induced high levels of antibodies in 90% of participants of a dose-escalating Phase 1/2 trial; and two vaccines entering Phase 1 trials: the self-amplifying mRNA- and adenovirus-vectored vaccine carrying the spike as well as other viral antigens (Gritstone), and the computationally optimized-epitope multivalent vaccine CoVepiT (OSE Immunotherapeutics).
Personalized cancer vaccine benefits ovarian cancer patients
Gemogenovatucel-T (Vigil, Gradalis) improved survival in homologous recombination-proficient ovarian cancer.Citation4 In 45 patients enrolled in a Phase 2b VITAL trial, the autologous T-cell immunotherapy increased relapse-free survival and overall survival by 2.5-to 3-fold compared to placebo. The treatment induced no grade 3/4 toxicities.
Gemogenovatucel-T consists of the patient’s own T-cells primed ex vivo by the resected tumor tissue and stimulated with GM-CSF. Furthermore, the procedure utilizes shRNA-mediated inhibition of furin, which is responsible for maintaining immune tolerance.
HIV vaccine induces broad immunity in an early trial
The HIV vaccine candidate eOD-GT8 was immunogenic in 97% of healthy adults participating in the randomized, double-blind, placebo-controlled Phase 1 IAVI G001 trial. The vaccine, which is adjuvanted with AS01B, is designed to elicit broadly neutralizing antibodies (bnAbs) through germline targeting of naïve B cells.
“We and others postulated many years ago that in order to induce bnAbs, you must start the process by triggering the right B cells – cells that have special properties giving them potential to develop into bnAb-secreting cells,” William Schief of Scripps Research Institute said. “In this trial, the targeted cells were only about one in a million of all naïve B cells. To get the right antibody response, we first need to prime the right B cells. The data from this trial affirm the ability of the vaccine immunogen to do this.”
Pancreatic cancer immunotherapy receives FDA’s OrphanDrug Designation
The US Food and Drug Administration (FDA) has granted its Orphan Drug Designation to the anti-CD39 MAb SRF617 (Surface Oncology) for treatment of pancreatic cancer. The move should facilitate the clinical development of this immunotherapeutic, which is in Phase 1 trials across a variety of solid tumors.
SRF617 targets the surface enzyme CD39, which is overexpressed in cancer to increase the adenosine-to-ATP ratio leading to immune suppression. In preclinical studies, SRF617 induced anti-tumor immunity both as a single agent and in combination with other treatments.
Guillain-Barré Syndrome is recognized as a rare adverse effect of herpes zoster vaccine
The FDA has added a Guillain-Barré Syndrome warning to the herpes zoster vaccine Shingrix (GSK). Surveillance studies have reported an increased risk of the neuro-autoimmune disease during 42 days following vaccination, although no causal relationship has yet been shown. The FDA continues to consider Shingrix, which is approved for adults 50 years and older, a safe vaccine, maintaining that its benefits far outweigh potential risks.
References
- Doria-Rose N, Suthar MS, Makowski M, O’Connell S, McDermott AB, Flach B, Ledgerwood JE, Mascola JR, Graham BS, Lin BC, et al.; mRNA-1273 Study Group. Antibody persistence through 6 months after the second dose of mRNA-1273 vaccine for Covid-19. N Engl J Med. 2021. doi:10.1056/NEJMc2103916.
- Kelly JC, Carter EB, Raghuraman N, Nolan LS, Gong Q, Lewis AN, Good M. Anti-SARS-CoV-2 antibodies induced in breast milk after Pfizer-BioNTech/BNT162b2 vaccination. Am J Obstet Gynecol. 2021; S0002-9378(21)00211–8.
- Gray KJ, Bordt EA, Atyeo C, Deriso E, Akinwunmi B, Young N, Medina Baez A, Shook LL, Cvrk D, James K, et al. COVID-19 vaccine response in pregnant and lactating women: a cohort study. Am J Obstet Gynecol. 2021; S0002-9378(21)00187-3. doi:10.1016/j.ajog.2021.03.023.
- Rocconi RP, Monk BJ, Walter A, Herzog TJ, Galanis E, Manning L, Bognar E, Wallraven G, Stanbery L, Aaron P, et al. Gemogenovatucel-T (Vigil) immunotherapy demonstrates clinical benefit in homologous recombination proficient (HRP) ovarian cancer. Gynecol Oncol. 2021; S0090-8258(21)00229–8. doi:10.1016/j.ygyno.2021.03.009.