Covid-19 vaccine approved for older children
The US Food and Drug Administration (FDA) has expanded the emergency-use indication for the Covid-19 vaccine BNT162b2 (Pfizer & BioNTech) to include adolescents aged 12-15 y. The decision is based on a >2,000-subject placebo-controlled trial showing that the safety in adolescents is comparable with that in adults. The vaccine has been used throughout the world in people aged ≥16 y.
The effectiveness of BNT162b2 might be increased with a longer interval between the doses, a study from UK suggests.Citation1 In a cohort of 175 elderly vaccinees, delaying the second dose by 8-9 weeks increased antibody levels by 3.5-fold, 2 weeks after completing the regimen. The vaccine doses are administered 3 weeks apart.
BNT162b2 has also proven effective against dangerous variants of the virus. A report from a mass vaccination campaign in Qatar estimated the effectiveness against the hypervirulent strains B.1.1.7 (UK) and B.1.351 (South Africa) at 90% and 75%, respectively.Citation2 These two variants have been responsible for almost all cases in the country since February.
Another study, which analyzed T-cell responses following vaccination with the two mRNA vaccines BNT162b2 and mRNA-1273 (Moderna), also showed comparable immunogenicity against both the parent strain and the two emerging viral lineages.Citation3 The results also suggest that one dose might suffice in subjects previously infected with Covid-19.
Another hypervirulent strain, B.1.617 spreading through India, was reported to be neutralized by sera from 25 individuals vaccinated with the mRNA vaccines, albeit to a lesser extent than the parent virus.Citation4
One dose of the adenovirus-vectored ChAdOx1-S (AstraZeneca) is sufficient to prevent 80% of deaths from Covid-19 and >70% of hospitalizations in those aged over 80 y, according to an analysis of the UK vaccination program, in which >27 million doses have been administered.Citation5
Meanwhile, the US Centers for Disease Control and Prevention lifted a restriction on other vaccines following immunization against Covid-19. For safety reasons, the agency recommended that no other vaccines should be administered within 2 weeks of Covid-19 vaccination. Abandoning this recommendation might boost routine vaccinations in the US.
Among other vaccines in development are the two-dose adjuvanted recombinant vaccine (Sanofi & GSK), which induced strong antibody responses in all >700 adult volunteers enrolled in a Phase 2 trial, and the single-dose intranasal vaccine AdCOVID (Altimmune), which induced sterilizing pulmonary immunity in a mouse challenge model.
Natural killer-cell-based immunotherapy shows some benefit in acute myeloid leukemia
Five of 12 patients with refractory acute myeloid leukemia achieved objective responses with complete leukemic myeloblast clearance in the bone marrow, according to interim data from two Phase 1 trials investigating the recombinant, induced pluripotent stem cell-derived, natural killer (NK)-cell immunotherapy (Fate Therapeutics).
The treatment consists of cycles of chemotherapy followed by immunotherapy with or without concomitant administration of IL-2. The cell line was engineered to express a high-affinity non-cleavable Fc receptor for increased binding to tumor-specific antibodies (the FT516 trial) and an additional IL-15 receptor fusion and CD38 deletion (the FT538 trial) for increased NK activity.
Bivalent oral norovirus vaccine for the elderly is tested in early-stage trial
Safety and immunogenicity of a tablet norovirus vaccine VXA-NVV-104 (Vaxart) will be tested in ~50 adults aged 55-80 y enrolled in a Phase 1 dose-escalation trial. The vaccine targets the norovirus capsid protein VP1 from two strains predominant in humans.
Norovirus is the leading cause of acute gastroenteritis globally. It accounts for ~60,000 hospitalizations, hundreds of deaths, and $10 billion in costs annually in the US alone.
Immune checkpoint inhibitor prolonged survival in triple-negative breast cancer
The PD-1 inhibitor pembrolizumab extended event-free survival in patients with high-risk early-stage triple-negative breast cancer, thus meeting primary endpoints of the Phase 3 KEYNOTE-522 trial. No survival data have been disclosed.
In the randomized placebo-controlled trial involving almost 1,200 patients, pembrolizumab was first administered together with chemotherapy prior to surgery and then as monotherapy after surgery.
The FDA had rejected pembrolizumab’s license application for this indication earlier in 2021 requesting more data.
24-valent pneumococcal vaccine was immunogenic in a preclinical trial
The 24-valent pneumococcal conjugate vaccine (PCV) VAX-24 (Vaxcyte) elicited non-inferior and superior immune responses compared with the licensed PCV-13 and 23-valent polysaccharide vaccine, respectively, in a rabbit model.Citation6 In the study, neutralizing antibodies and anti-capsular IgGs were measured 2 weeks following the vaccine regimen, which consists of two doses 3 weeks apart.
Anti-depressant drug potentiated checkpoint inhibition immunotherapy in a preclinical model
The monoamine oxidase A inhibitor phenelzine induced antitumor T-cell immunity in mice with melanoma and colon cancer.Citation7 Moreover, the drug, which is approved for treatment of depression, synergized with immune checkpoint inhibitors to suppress tumor growth.
Database search revealed that high expression of monoamine oxidase A correlates with lower levels of tumor-infiltrating lymphocytes and worse prognosis in patients with a variety of cancers.
The authors conclude that monoamine oxidase A is an immune checkpoint, and phenelzine could be repurposed for cancer immunotherapy.
Disclosure statement
No potential conflict of interest was reported by the author(s).
References
- Parry HM, Bruton R, Stephens C, Brown K, Amirthalingam G, Hallis B, Otter A, Zuo J, Moss P. Extended interval BNT162b2 vaccination enhances peak antibody generation in older people. MedRxiv [prepr]. 2021. doi:10.1101/2021.05.15.21257017.
- Abu-Raddad LJ, Chemaitelly H, Butt AA, National Study Group for COVID-19 Vaccination. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. N Engl J Med. 2021. doi:10.1056/NEJMc2104974.
- Neidleman J, Luo X, McGregor M, Xie G, Murray V, Greene WC, Lee SA, Roan NR. mRNA vaccine-induced SARS-CoV-2-specific T cells recognize B.1.1.7 and B.1.351 variants but differ in longevity and homing properties depending on prior infection status. BioRxiv [prepr]. 2021. doi:10.1101/2021.05.12.443888.
- Edara VV, Lai L, Sahoo MK, Floyd K, Sibai M, Solis D, Flowers MW, Hussaini L, Ciric CR, Bechnack S, et al. Infection and vaccine-induced neutralizing antibody responses to the SARS-CoV-2 B.1.617.1 variant. BioRxiv [prepr]. 2021. doi:10.1101/2021.05.09.443299.
- Bernal JL, Andrews N, Gower C, Stowe J, Tessier E, Simmons R, Ramsay M. Effectiveness of BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on mortality following COVID-19. KnowledgeHub [prepr]. 2021; [accessed May 20]. https://khub.net/documents/135939561/430986542/Effectiveness+of+BNT162b2+mRNA+vaccine+and+ChAdOx1+adenovirus+vector+vaccine+on+mortality+following+COVID-19.pdf/9884d371-8cc8-913c-211c-c2d7ce4dd1c3.
- Fairman J, Agarwal P, Barbanel S, Behrens C, Berges A, Burky J, Davey P, Fernsten P, Grainger C, Guo S, et al. Non-clinical immunological comparison of a Next-Generation 24-valent pneumococcal conjugate vaccine (VAX-24) using site-specific carrier protein conjugation to the current standard of care (PCV13 and PPV23). Vaccine. 2021;S0264-410X:00374–1.
- Wang X, Li B, Kim YJ, Wang YC, Li Z, Yu J, Zeng S, Ma X, Choi IY, Di Biase S, et al. Targeting monoamine oxidase A for T cell-based cancer immunotherapy. Sci Immunol. 2021;6(59):eabh2383. doi:10.1126/sciimmunol.abh2383.