Covid-19 vaccine is safe and immunogenic in children
The SARS-CoV-2 vaccine BNT162b2 (Pfizer & BioNTech) has demonstrated safety in children aged 5–11 y, as well as immunogenicity comparable to older cohorts. A total of 2,300 subjects received two doses 3 weeks apart in a Phase 2/3 trial. The dosage level used for children was 1/3.
The US Food and Drug Administration has granted emergency-use authorization to a third dose of BNT162b2 for adults ≥65 y of age and those at higher risk of Covid-19 complications due to medical condition or high-exposure occupation.
Other countries, such as Israel and Germany, are offering a booster dose for all eligible subjects, and two studies from Israel showed a significant benefit. Three doses of the vaccine decreased the risk of testing positive by ~50%Citation1and severe illness by >90%Citation2 compared to two doses.
A booster dose is also being tested for the single-dose Ad26.COV2.S vaccine (J&J). In the Phase 3 ENSEMBLE trial, the second dose administered 2 months after the first increased protection from symptomatic and severe disease to 94% and >99%, respectively, 2 weeks later. The efficacies were 66% and 85% after one dose.
Several studies presented at the European Society for Medical Oncology congress showed that Covid-19 vaccines are safe and effective in cancer patients both on and off treatment. Cancer patients had been excluded from earlier trials.
India has approved a new Covid-19 vaccine, the domestic DNA vaccine ZyCoV-D, which showed 67% efficacy against symptomatic disease in clinical trials. ZyCoV-D, which is administered intradermally with a jet injector, is the first approved DNA vaccine. This class has several advantages over mRNA vaccines, including greater stability and easier production.
Other Covid-19 vaccines in clinical development include the inactivated, adjuvanted vaccine VLA2001 (Valneva), which has started a Phase 3 trial in adolescents and a booster trial for previously enrolled individuals, and the lipid nanoparticle-formulated mRNA vaccine (Sanofi), which was safe and induced neutralizing antibodies in 90–100% of subjects enrolled in a dose-escalation Phase 1/2 trial.
Neoantigen vaccine improves survival in advanced non-small-cell lung cancer
The cancer vaccine Tedopi (OSE Immunotherapeutics) increased median overall survival to 11 months, compared to 7.5 months after standard-of-care chemotherapy, in patients with advanced non-small-cell lung cancer (NSCLC) who had failed prior checkpoint inhibition immunotherapy. The randomized Phase 3 Atalante 1 trial enrolled 220 HLA-A2-positive subjects.
Tedopi, which contains a set of tumor-associated antigens, is designed to elicit T-cell responses in otherwise ‘immunologically cold’ tumors.
Progress in the development of RSV vaccine
The pentavalent RSV vaccine candidate MVA-BN RSV (Bavarian Nordic) was safe and protective in a Phase 2 human challenge trial. 60 adult volunteers were randomized to receive the vaccine or placebo and challenged intranasally with type A RSV one month later. Viral load and clinical symptoms were reduced in the experimental cohort, and the vaccine efficacy was estimated at 80%.
Another RSV vaccine candidate, the VLP vaccine IVX-121 (Icosavax), has entered clinical testing. The randomized, placebo-controlled Phase 1/1b trial will evaluate the safety and immunogenicity of both adjuvanted and non-adjuvanted formulations in 300 adults, including older adults. IVX-121 targets the pre-fusion F antigen of the virus.
Checkpoint inhibitors beneficial in two cancer indications
The anti-PD-L1 MAb atezolizumab (Tecentriq, Roche) decreased the risk of relapse or death by 34%, compared to best supportive care, in patients with advanced NSCLC and high PD-L1 levels.Citation3 The open-label, randomized Phase 3 IMpower010 trial enrolled 1,000 subjects with disease recurrence after surgery and cisplatin chemotherapy.
Combination of PD-1 and CTLA-4 inhibitors balstilimab and zalifrelimab (both Agenus) induced responses in 26% of 125 evaluable patients with recurrent or metastatic cervical cancer. Complete responses were reported for 9% of participants. Median duration of response was not reached after a 20-month follow-up.
PCV-20 can be co-administered with influenza vaccine, study shows
The combination of the 20-valent pneumococcal conjugate vaccine Prevnar 20 (Pfizer) and quadrivalent, adjuvanted seasonal influenza vaccine Fluad (Seqirus) was equally safe and immunogenic as when the vaccines were administered 1 month apart. The Phase 3 trial enrolled >1,700 participants ≥65 y old.
Prevnar 20 targets the 13 strains included in its predecessor Prevnar 13 and seven additional strains associated with antibiotic resistance and invasive disease with high fatality rates. The vaccine consists of capsule polysaccharides from Streptococcus pneumoniae each conjugated to a diphtheria toxoid.
Ebola two-vaccine regimen is strongly immunogenic
The combination of Ebola vaccines Ad26.ZEBOV (Zabdeno, J&J) followed by MVA-BN-Filo (Mvabea, Bavarian Nordic) 8 weeks later induced antibodies against the Zaire strain in 98% of tested subjects, as measured 3 weeks after the second dose.Citation4,Citation5 The data come from two clinical trials testing the regimen in adults and children ≥1 y old.
In both cohorts, the vaccines were safe with no serious adverse events. In adults, immunity lasted at least 2 y, whereupon a booster dose induced additional responses within 1 week.
Opioid vaccine has initiated a Phase 1 trial
Forty-five adult opioid users are being enrolled in a clinical trial testing an anti-oxycodone vaccine. Oxycodone, which is responsible for euphoric feelings in users of heroin and some painkillers, can lead to severe toxicity and death in overdosed patients. The vaccine is designed to prevent the substance from reaching the brain.
Lyme disease vaccine completes Phase 2 trial
The Lyme disease vaccine candidate VLA15 (Valneva) elicited strong antibody responses to all targeted serotypes in the randomized, placebo-controlled Phase 2 VLA15-202 trial. A booster dose, which was administered after 18 months to a trial sub-cohort due to waning immunity, further increased responses three- to four-fold.
The dose-escalation VLA15-202 trial, which enrolled 250 healthy adults up to 65 y of age, showed that the vaccine was safe and immunogenic at all dosage levels.
VLA15 is an aluminum-adjuvanted hexavalent subunit vaccine targeting the outer membrane protein OspA from Borrelia burgdorferi, the causative agent of Lyme disease.
Disclosure statement
No potential conflict of interest was reported by the author(s).
References
- Patalon T, Gazit S, Pitzer VE, Prunas O, Warren JL, Weinberger DM. Short term reduction in the odds of testing positive for SARS-CoV-2; a comparison between two doses and three doses of the BNT162b2 vaccine. MedRxiv [preprint]. 2021. doi:10.1101/2021.08.29.21262792.
- Bar-On YM, Goldberg Y, Mandel M, Bodenheimer O, Freedman L, Kalkstein N, Mizrahi B, Alroy-Preis S, Ash N, Milo R, et al. BNT162b2 vaccine booster dose protection: a nationwide study from Israel. MedRxiv [preprint]. 2021. doi:10.1101/2021.08.27.21262679.
- Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, et al. IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344–2. doi:10.1016/S0140-6736(21)02098-5.
- Ishola D, Manno D, Afolabi MO, Keshinro B, Bockstal V, Rogers B, Owusu-Kyei K, Serry-Bangura A, Swaray I, Lowe B, et al. EBL3001 study group. Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial. Lancet Infect Dis. 2021;S1473–3099(21)00125–0.
- Afolabi MO, Ishola D, Manno D, Keshinro B, Bockstal V, Rogers B, Owusu-Kyei K, Serry-Bangura A, Swaray I, Lowe B, et al. EBL3001 study group. Safety and immunogenicity of the two-dose heterologous Ad26. ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial. Lancet Infect Dis. 2021;S1473–3099(21)00128–6.