The recent study conducted by scientists at the Garvan Institute of Medical Research and the Kirby Institute at UNSW Sydney has shed new light on how vaccination site can impact the effectiveness of immune response. The research, published in the journal Cell, found that receiving a booster vaccine in the same arm as your first dose can generate a more effective immune response more quickly.

The study’s findings are based on observations made in mice and validated in human participants. It was discovered that when a vaccine is administered, specialized immune cells called macrophages become “primed” inside lymph nodes. These primed macrophages then direct the positioning of memory B cells to respond more effectively to the booster when given in the same arm.

“This is a fundamental discovery in how the immune system organizes itself to respond better to external threats,” says Professor Tri Phan, Director of the Precision Immunology Program at Garvan and co-senior author. “Nature has come up with this brilliant system, and we’re just now beginning to understand it.”

The researchers used state-of-the-art intravital imaging at Garvan to observe how memory B cells migrate to the outer layer of the local lymph node, where they interact closely with macrophages that reside there. When a booster was given in the same location, these primed macrophages efficiently captured the antigen and activated the memory B cells to make high-quality antibodies.

Dr Rama Dhenni, co-first author of the study, notes, “Macrophages are known to gobble up pathogens and clear away dead cells, but our research suggests that the ones in the lymph nodes closest to the injection site also play a central role in orchestrating an effective vaccine response the next time around. So location does matter.”

A clinical study conducted by the Kirby Institute with 30 volunteers receiving the Pfizer-BioNTech COVID-19 mRNA vaccine validated these findings. Participants who received their booster dose in the same arm as their first dose produced neutralizing antibodies against SARS-CoV-2 significantly faster, within the first week after the second dose.

“These antibodies from the same-arm group were also more effective against variants like Delta and Omicron,” says Dr Mee Ling Munier, co-senior author. “By four weeks, both groups had similar antibody levels, but that early protection could be crucial during an outbreak.”

The study’s findings offer a promising new approach for enhancing vaccine effectiveness, particularly in the context of rapidly mutating viruses where speed of response matters.

“If we can understand how to replicate or enhance the interactions between memory B cells and these macrophages, we may be able to design next-generation vaccines that require fewer boosters,” says Professor Phan.

A recent study from researchers at George Washington University has shed new light on the relationship between nasal bacteria and COVID-19 risk. Published in EBioMedicine, the research reveals that certain types of nasal bacteria can affect the levels of key proteins the virus needs to enter human cells, offering a crucial insight into why some people are more vulnerable to COVID-19 than others.

The study analyzed nasal swab samples from over 450 individuals, including those who later tested positive for COVID-19. The researchers found that those who became infected had higher levels of gene expression for two key proteins: ACE2 and TMPRSS2. ACE2 allows the virus to enter nasal cells, while TMPRSS2 helps activate the virus by cleaving its spike protein.

Those with high expression for these proteins were more than three times as likely to test positive for COVID-19, while those with moderate levels had double the risk. Notably, men with higher levels of these proteins were more likely to get infected, indicating that elevated protein levels may present a greater risk for men.

To understand what could impact the expression levels of these viral entry proteins, the researchers turned to the nasal microbiome – the diverse community of bacteria that naturally reside in the nose. They found that certain nasal bacteria may affect the expression levels of ACE2 and TMPRSS2, influencing the respiratory tract’s susceptibility to COVID-19.

The study identified three common nasal bacteria – Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis/nonliquefaciens – that were linked to higher expression levels of ACE2 and TMPRSS2 and increased COVID-19 risk. On the other hand, Dolosigranulum pigrum, another common type of nasal bacteria, was connected to lower levels of these key proteins and may offer some protection against the virus.

The findings offer new potential ways to predict and prevent COVID-19 infection. The study suggests that monitoring ACE2 and TMPRSS2 gene expression could help identify individuals at higher risk for infection. The research also highlights the potential of targeting the nasal microbiome to help prevent viral infections.

“We’re only beginning to understand the complex relationship between the nasal microbiome and our health,” said Cindy Liu, associate professor of environmental and occupational health at the GW Milken Institute School of Public Health. “This study suggests that the bacteria in our nose – and how they interact with the cells and immune system in our nasal cavity – could play an important role in determining our risk for respiratory infections like COVID-19.”

The team plans to explore whether modifying the nasal microbiome, such as through nasal sprays or live biotherapeutics, could reduce the risk of infection – potentially paving the way for new ways to prevent respiratory viral infections in future pandemics.

A team of researchers led by Dr. KIM V. Narry has made a groundbreaking discovery in understanding how mRNA vaccines are delivered, processed, and degraded within cells. Their study, published in Science, sheds light on the cellular mechanisms that affect the function of mRNA vaccines and therapeutics, paving the way for more effective treatments.

Messenger RNA (mRNA) plays a crucial role in mRNA vaccines, such as those used for COVID-19, and is also a promising tool for treating diseases like cancer and genetic disorders. When foreign mRNA enters cells, it must evade the body’s natural defense mechanisms to be effective. However, the detailed mechanisms by which mRNA is regulated inside cells have remained largely unknown.

The research team employed CRISPR-based knockout screening to identify the cellular factors involved in the delivery of mRNA into cells. This approach revealed three key factors that facilitate the cellular uptake or surveillance of exogenous mRNAs:

1. Heparan sulfate (HSPG), a sulfated glycoprotein on the cell surface, plays a crucial role in attracting LNPs and facilitating mRNA entry into the cell.
2. V-ATPase, a proton pump at the endosome, acidifies the vesicle and causes LNPs to become positively charged, enabling them to temporarily disrupt the endosomal membrane and release the mRNA into the cytoplasm.
3. TRIM25, a protein involved in the cellular defense mechanism, binds to and induces the rapid degradation of exogenous mRNAs, preventing their function.

The study highlights that mRNA molecules containing a special modification called N1-methylpseudouridine (m1Ψ) can evade TRIM25 detection, enhancing the stability and effectiveness of mRNA vaccines. This discovery emphasizes the importance of this modification in enhancing the therapeutic potential of mRNA-based treatments.

Additionally, the research demonstrates that proton ions serve as immune signaling molecules, providing new insights into how cells protect themselves from foreign RNA.

Dr. KIM V. Narry emphasized the importance of understanding these processes, stating, “Understanding how cells respond to mRNA vaccines is key to improving mRNA therapeutics. To develop effective RNA treatments, we need to find ways to bypass the cellular defense mechanisms and harness the endosomal system effectively.”

This research paves the way for more efficient mRNA vaccine delivery and offers a framework for future development of RNA-based therapies. The findings underscore the critical importance of early intervention and provide new directions for developing more effective treatments for a variety of diseases.