Research Roundup: Why mRNA Vaccines are So Good Against Severe COVID-19 and More – BioSpace

Not surprisingly, theres still plenty of interesting research coming out about COVID-19, but the end of 2021 also provided exciting science in other areas. Heres a look.

Scientists out ofWashington University School of Medicinewanted to understandwhy the mRNA vaccines by Pfizer-BioNTech and Moderna are so effective at preventing severe disease. Even in the face of Omicron, which is particularly good at evading immune protection, people vaccinated with the two mRNA vaccines appear to be strongly protected against hospitalization and death from COVID-19. The researchers, along withSt. Jude Childrens Research Hospital,found that the Pfizer-BioNTech strongly and persistently activated a specific type of helper immune cell known as T follicular helper cells. These immune cells help antibody-producing cells to create large amounts of increasingly powerful antibodies and drives development of some forms of immune memory. They published their research in the journalCell.

The longer the T follicular helper cells provide help, the better the antibodies are and the more likely you are to have a good memory response, said Dr. Philip Mudd, co-corresponding author and assistant professor of emergency medicine at Washington University. In this study, we found that these T follicular helper cell responses just keep going and going. And whats more, some of them are responding to one part of the viruss spike protein that has very little variation in it. With the variants, especially Delta and now Omicron, weve been seeing some breakthrough infections, but the vaccines have held up very nicely in terms of preventing severe disease and death. I think this strong T follicular helper response is part of the reason why the mRNA vaccines continue to be so protective.

Generally, the first antibodies generated in response to an infection or vaccine arent very high quality. The researchers say B cells need to go through a sort of boot camp in the lymph nodes before they can generate very powerful antibodies. T follicular helper cells, they note, are the drill sergeants of the boot camps. The helper cells give instructions to the antibody-producing cells on how to make even better antibodies and then encourage the best to multiple and sometimes become long-lived memory B cells.

More Data Omicron Evades Immune Protection

The growing body of evidence that the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, can evade immunity created with vaccines and natural infection gained yet more support. Research out ofColumbia University Irving Medical Centerand theUniversity of Hong Kongtested antibodiesgenerated by vaccination and their ability to neutralize Omicron in laboratory assays using live viruses and pseudoviruses that mimic Omicron. They found that antibodies from people double-vaccinated by the Moderna, Pfizer-BioNTech, AstraZeneca-Oxford and Johnson & Johnson vaccines were significantly less effective against Omicron compared to the wildtype Wuhan strain. And the antibodies from people who were naturally infected were even less effective. The booster shots helped, but still showed decreased neutralizing activity.

Microorganism Helps Understand Cancer Resistance

Scientists atArizona State Universitydescribethe ability of a microorganism,Trichoplax adhaerens, to repair its DNA, even from significant radiation exposure. It also can extrude injured cells, which then die. The research provides insights into natural cancer-suppression mechanisms in a wide range of lifeforms.T. adhaerensis the simplest multicellular organism on Earth and is native to the Red Sea and other warm waters. In addition, its complete genome has been sequenced. No cancer has ever been seen in the organism. They can withstand radiation by increasing the expression of particular genes involved in DNA repair and genes linked with apoptosis (cell death). Their ability to extrude damaged cells, such as precancerous cells, may also explain their ability to fend off cancer.

Epigenetics of Microglia in the Brain

Epigenetics is the study of how the environment or behaviors change the ways genes work. In other words, although genes are sometimes turned on and sometimes turned off, epigenetics is the study of what turns them on or off and any in between states. Microglia are a type of immune cell found in the brain and central nervous system. They were thought for a long time to be activated or inactivated, and their effects were either pro-inflammatory or neuroprotective. But researchers at theIcahn School of Medicine at Mount Sinai, led by Fatemeh Haghighi, Professor of Neuroscience and Psychiatry,isolatedmicroglia cells from post-mortem human brain tissue from 22 people. The patients had a variety of illnesses while alive: one with schizophrenia, 13 with mood disorders, and 8 with no psychiatric disorders. The researchers used genome-scale methylation microarrays to analyze the microglia. Methylation is one form of epigenetic control of genes. They found that microglia demonstrated DNA methylation profiles distinct from other CNS cells, which was expected. But they also found differences in the methylation levels of microglia individually, which suggested that microglial methylation may play a role in a variety of psychiatric disorders.

Antibiotic-Antioxidant Combo Slows Dementia in Mice

Dementia, such as Alzheimers, is believed to be caused by an accumulation of proteins called beta-amyloid, tau and alpha-synuclein, which collect in the brain and form oligomers. Researchers atOsaka City University Graduate School of Medicinehad previouslydescribedthe use of the antibiotic rifampicin to remove oligomers from the brain, which improved cognitive function. But rifampicin can cause liver damage and other side effects. Resveratrol is a naturally occurring plant antioxidant that is used as a supplement in the U.S. and Europe. The researchers thought they could combine the positive effects of rifampicin while fighting its negative effects with resveratrol. They used a fixed dose combination intranasally five days a week for four weeks on mice models of Alzheimers, frontotemporal dementia, and dementia with Lewy bodies. The drugs improved cognition, inhibited oligomer accumulation, and restored synaptophysin levels, which facilitate synapses. In addition, the blood levels of liver enzymes that typically increase with rifampicin stayed normal. A bonus was they observed increased levels of brain-derived neurotrophic factor (BNDF) expression in the hippocampus, which was not typically seen with only rifampicin.

Severe COVID-19 Negatively Affects B-Cell Memory

Researchers at theUniversity of Texas Health Science Centerat San Antoniofoundthat patients who recovered from less-severe cases of COVID-19 had B cells that had better immune memory of the viruss spike protein compared to patients who recovered from severe COVID-19. The researchers analyzed blood samples a month after symptom onset and five months post-onset. At the one-month mark, a significant percentage of spike-specific B cells were active. But in eight people who recovered from less-severe disease, they had increased expression of markers linked with durable B-cell memory compared to people who recovered from severe disease. The markers included T-bet and FcRL5.

The increased percentage of B cells associated with long-lived immunity in non-severe COVID-19 patients may have consequences for long-term immunity against SARS-CoV-2 re-infection or severity of the resulting disease, the authors wrote.

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Research Roundup: Why mRNA Vaccines are So Good Against Severe COVID-19 and More - BioSpace