Covid-19 vaccination campaign stumbles as two vaccines show rare severe side effects
Two approved adenovirus-based vaccines (J&J and AstraZeneca) have been implicated in severe brain clots. The European Medicines Agency received reports of 169 cases following 34 million administered doses of the AZ vaccine and recommended its continued use, as the risk of dying from Covid-19 is far greater than that from rare adverse events. Nonetheless, Denmark has stopped using the vaccine, and the EU is considering to not extend contracts with J&J and AZ. Six cases of cerebral thrombosis have been reported in the US from ~7 million people who received the J&J vaccine. The Centers for Disease Control and Prevention is reviewing the data while the rollout of this vaccine has been paused.
The World Health Organization (WHO) has called attention to a “shocking imbalance” in the distribution of Covid-19 vaccines around the world. Although the COVAX initiative has distributed 38 million vaccine doses to poorer countries, the rich ones still have a disproportionate share. “On average in high-income countries, almost one in four people have received a Covid-19 vaccine. In low-income countries, it is one in more than 500,” WHO Director General Tedros Adhanom Ghebreyesus said.
Meanwhile, the inactivated vaccine CoronaVac (Sinovac) has been shown to be 50% efficacious in preventing infection by the hyper-transmissible SARS-CoV-2 strain P.1 in Brazil, where this lineage dominates. The efficacy rate is similar to that against the parent strain. Although much lower in its effectiveness than other vaccines in use, it still could slow the spread of Covid-19 in one of the worst affected countries.
While most current vaccines require two doses to attain full protection in disease-naïve individuals, one dose might be sufficient in subjects who have had SARS-CoV-2 infection prior to vaccination. According to a report on the two marketed mRNA vaccines (Pfizer/BioNTech and Moderna), there is little benefit of receiving the second dose in previously infected people.Citation1
Among other SARS-CoV-2 vaccines in development is another mRNA candidate MRT5500 (Translate Bio), which has shown immunogenicity and protective efficacy in mouse and primate models,Citation2 and a recombinant vaccine, in which E. coli expresses a surface fusion peptide based on a conserved coronaviral sequence. This vaccine, which is easily produced and could solve many logistical hurdles, was protective in a porcine model.Citation3
Personalized cancer vaccine was safe in an early trial
The OpenVax personalized cancer vaccine treatment raised no safety concerns in a Phase 1 trial involving 13 patients with various types of cancer. The approach identifies neoantigens by comparing patient’s tumor and germline DNA, and predicts the most immunogenic ones in silico. Ten doses of the vaccine adjuvanted with poly-ICLC were administered over 6 months following standard-of-care treatment (surgery for solid tumors and bone marrow transplant for multiple myeloma). At a mean follow-up time of ~2.5 years, four patients
Unlike in most personalized approaches, the vaccine was administered immediately after the first-line treatment, when there is little residual disease. This might increase its efficacy, according to the authors from Icahn School of Medicine at Mount Sinai.
650,000 children have been vaccinated against malaria
1.7 million doses of the RTS,S malaria vaccine (GSK) have been administered in a pilot program in Malawi, Ghana and Kenya. There have been 650,000 children reached in the campaign, which is almost double the intended number at the start two years ago, attesting to a strong community demand. The pilot program is designed to yield data on vaccine safety, its impact on child mortality and parental compliance.
The recombinant RTS,S, which is administered in four doses, is the first malaria vaccine to show efficacy in clinical trials. It was able to prevent ~40% of cases and 30% of severe malaria, which kills almost half a million people annually.
Atezolizumab combination shows signs of benefit in glioblastoma
The PD-L1-specific MAb atezolizumab combined with the AKT inhibitor ipatasertib (both Roche) induced complete remission in one of 10 patients with recurrent glioblastoma enrolled in the Phase 1 Ice-CAP trial. One participant reported a partial remission 22 months after treatment.
Patients with recurrent glioblastoma have poor prognosis and very few treatment options. “Brain cancer is able to evade the immune system in complex ways and, until now, immunotherapy has not worked. However, by uncloaking the disease using a new drug called ipatasertib, this study suggests that we could make some brain cancers vulnerable to atezolizumab,” study leader Juanita Lopez of Royal Marsden NHS Foundation Trust said.
References
- Goel RR, Apostolidis SA, Painter MM, Mathew D, Pattekar A, Kuthuru O, Gouma S, Hicks P, Meng W, Rosenfeld AM, et al. Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. Sci Immunol. 2021;6(58):eabi6950. doi:10.1126/sciimmunol.abi6950.
- Kalnin KV, Plitnik T, Kishko M, Zhang J, Zhang D, Beauvais A, Anosova NG, Tibbitts T, DiNapoli J, Ulinski G, et al. Immunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models. NPJ Vaccines. 2021;6(1):61. doi:10.1038/s41541-021-00324-5.
- Maeda DLNF, Tian D, Yu H, Dar N, Rajasekaran V, Meng S, Mahsoub HM, Sooryanarain H, Wang B, Heffron CL, et al. Killed whole-genome reduced-bacteria surface-expressed coronavirus fusion peptide vaccines protect against disease in a porcine model. Proc Natl Acad Sci U S A. 2021;118(18):e2025622118. doi:10.1073/pnas.2025622118.