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Study shows why second dose of COVID-19 vaccine shouldn’t be skipped

The second dose of a COVID-19 vaccine induces a powerful boost to a part of the immune system that provides broad antiviral protection, according to a study led by investigators at the Stanford University School of Medicine.

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The second dose of a COVID-19 vaccine induces a powerful boost to a part of the immune system that provides broad antiviral protection, according to a study led by investigators at the Stanford University School of Medicine.

The finding strongly supports the view that the second shot should not be skipped.

“Despite their outstanding efficacy, little is known about how exactly RNA vaccines work,” said Bali Pulendran, PhD, professor of pathology and of microbiology and immunology. “So we probed the immune response induced by one of them in exquisite detail.”

The study, published in Nature, was designed to find out exactly what effects the vaccine, marketed by Pfizer Inc., has on the numerous components of the immune response.

The researchers analyzed blood samples from individuals inoculated with the vaccine. They counted antibodies, measured levels of immune-signaling proteins and characterized the expression of every single gene in the genome of 242,479 separate immune cells’ type and status.

“The world’s attention has recently been fixed on COVID-19 vaccines, particularly on the new RNA vaccines,” said Pulendran, the Violetta L. Horton Professor II.

He shares senior authorship of the study with Kari Nadeau, MD, PhD, the Naddisy Foundation Professor of Pediatric Food, Allergy, Immunology, and Asthma and professor of pediatrics, and Purvesh Khatri, PhD, associate professor of biomedical informatics and of biomedical data science. The study’s lead authors are Prabhu Arunachalam, PhD, a senior research scientist in Pulendran’s lab; medical student Madeleine Scott, PhD, a former graduate student in Khatri’s lab; and Thomas Hagan, PhD, a former postdoctoral scholar in Pulendran’s Stanford lab and now an assistant professor at the Yerkes National Primate Research Center in Atlanta.

Uncharted territory

“This is the first time RNA vaccines have ever been given to humans, and we have no clue as to how they do what they do: offer 95% protection against COVID-19,” said Pulendran.

Traditionally, the chief immunological basis for approval of new vaccines has been their ability to induce neutralizing antibodies: individualized proteins, created by immune cells called B cells, that can tack themselves to a virus and block it from infecting cells.

“Antibodies are easy to measure,” Pulendran said. “But the immune system is much more complicated than that. Antibodies alone don’t come close to fully reflecting its complexity and potential range of protection.”

Pulendran and his colleagues assessed goings-on among all the immune cell types influenced by the vaccine: their numbers, their activation levels, the genes they express and the proteins and metabolites they manufacture and secrete upon inoculation.

One key immune-system component examined by Pulendran and his colleagues was T cells: search-and-destroy immune cells that don’t attach themselves to viral particles as antibodies do but rather probe the body’s tissues for cells bearing telltale signs of viral infections. On finding them, they tear those cells up.

In addition, the innate immune system, an assortment of first-responder cells, is now understood to be of immense importance. It’s the body’s sixth sense, Pulendran said, whose constituent cells are the first to become aware of a pathogen’s presence. Although they’re not good at distinguishing among separate pathogens, they secrete “starting gun” signaling proteins that launch the response of the adaptive immune system — the B and T cells that attack specific viral or bacterial species or strains. During the week or so it takes for the adaptive immune system to rev up, innate immune cells perform the mission-critical task of holding incipient infections at bay by gobbling up — or firing noxious substances, albeit somewhat indiscriminately, at — whatever looks like a pathogen to them.

A different type of vaccine

The Pfizer vaccine, like the one made by Moderna Inc., works quite differently from the classic vaccines composed of live or dead pathogens, individual proteins or carbohydrates that train the immune system to zero in on a particular microbe and wipe it out. The Pfizer and Moderna vaccines instead contain genetic recipes for manufacturing the spike protein that SARS-CoV-2, the virus that causes COVID-19, uses to latch on to cells it infects.

In December 2020, Stanford Medicine began inoculating people with the Pfizer vaccine. This spurred Pulendran’s desire to assemble a complete report card on the immune response to it.

The team selected 56 healthy volunteers and drew blood samples from them at multiple time points preceding and following the first and second shots. The researchers found that the first shot increases SARS-CoV-2-specific antibody levels, as expected, but not nearly as much as the second shot does. The second shot also does things the first shot doesn’t do, or barely does.

“The second shot has powerful beneficial effects that far exceed those of the first shot,” Pulendran said. “It stimulated a manifold increase in antibody levels, a terrific T-cell response that was absent after the first shot alone, and a strikingly enhanced innate immune response.”

Unexpectedly, Pulendran said, the vaccine — particularly the second dose — caused the massive mobilization of a newly discovered group of first-responder cells that are normally scarce and quiescent.

First identified in a recent vaccine study led by Pulendran, these cells — a small subset of generally abundant cells called monocytes that express high levels of antiviral genes — barely budge in response to an actual COVID-19 infection. But the Pfizer vaccine induced them.

This special group of monocytes, which are part of the innate museum, constituted only 0.01% of all circulating blood cells prior to vaccination. But after the second Pfizer-vaccine shot, their numbers expanded 100-fold to account for a full 1% of all blood cells. In addition, their disposition became less inflammatory but more intensely antiviral. They seem uniquely capable of providing broad protection against diverse viral infections, Pulendran said.

“The extraordinary increase in the frequency of these cells, just a day following booster immunization, is surprising,” Pulendran said. “It’s possible that these cells may be able to mount a holding action against not only SARS-CoV-2 but against other viruses as well.”

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How to help children build a growth mindset

Consider these three tips to help children build a growth mindset.

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A new year is a perfect time to consider the habits you want to keep and the ones you’d like to develop. One resolution to consider is helping your children develop a growth mindset this year.

“We know one of the greatest boosts to parents’ confidence over the past year came from knowing their children’s whole selves are being nurtured, and we want to see that trend continue,” said Carter Peters from KinderCare Learning Center’s education team. “A growth mindset helps children try new things despite fear of failure. It’s the kind of thinking that allows inventors and creative thinkers to get excited about trying something new and ensures they have the cognitive flexibility and problem-solving skills to work through hurdles.”

Adults can often easily spot when children are engaged in creative thinking and prideful of their work, but that confidence may be lost as failures turn into insecurities. By nurturing a growth mindset and showing children they can learn and develop new skills in any area, it better sets them up for long-term success.

Consider these three tips to help children build a growth mindset:

Photo by Markus Spiske from Unsplash.com

1. Praise effort

It’s easy to fall into the habit of praising successes. However, praising effort encourages children to try new things without the fear of failing. It also teaches children personal growth and achievement are possible, even if their overall effort wasn’t a success.

“Young children often get excited to try something new,” Peters said. “By praising effort and showing children they’ll still be loved and valued despite the outcome, you can reframe how they approach challenges and teach them that difficult doesn’t mean impossible.”

2. Encourage the process

People often withhold praise until there’s a result, which leads children to hurriedly scribble a picture to hold up for a “good job” instead of taking time to focus on their efforts. When children know adults will encourage them during the process, instead of only upon the achievement, they’re more likely to try new things or master a new skill. For example, try providing encouragement such as, “I can see you’re focused on drawing that tree. It looks so lifelike because you’re putting so much thought into what you’re doing.” Once their project is finished, continue the encouragement by hanging up their artwork or school projects in a prominent place.

3. Model a growth mindset

You can model a growth mindset for children by narrating your actions when you are facing a challenge: “I am having a difficult time putting this shelf together, but it’s OK. I’ll take a break then read the instructions again.” Remove negative words from your vocabulary, such as “I can’t” or “I’m stupid.” Even when you are joking, children may not be able to tell the difference. You can also ask your children to join you in problem-solving. Take time to hear their ideas and try them even if you think they won’t work. This not only supports the development of their growth mindset, but the quality time and encouragement reinforces their sense of self-worth and builds confidence.

For more tips to help children develop a growth mindset, visit kindercare.com.

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Signs of a Healthy Marriage

Although there are many different ways to define a healthy marriage, these three qualities are essential for any lasting and fulfilling relationship.

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A healthy marriage is built on trust, respect, and communication. Couples with these qualities in their relationship tend to be more satisfied with their marriage and overall life. They also report feeling closer to their partner and having stronger well-being. With 2.3 out of every 1000 people in the US experiencing divorce in 2022, it is important to frequently check in on the health of your marriage.

Although there are many different ways to define a healthy marriage, these three qualities are essential for any lasting and fulfilling relationship.

Signs of a Healthy Marriage

A healthy marriage is built on trust, communication, and mutual respect. If you and your partner can effectively communicate and share a mutual level of respect, then your relationship is off to a good start. Trust is also important in a healthy marriage, as it allows you and your partner to feel secure in your relationship and rely on each other.

Many other signs can indicate whether or not a marriage is healthy. For example, couples who can spend quality time together and enjoy shared activities usually do well. Couples who can openly discuss their relationship with each other and work through difficulties together are also more likely to have a happy and healthy marriage. Finally, marriages, where both partners feel like they can be themselves without judgment from their spouse tend to be the strongest and most lasting.

Freedom to be yourself

In a healthy marriage, partners feel free to be themselves. They don’t have to put on a facade or pretend to be someone they’re not. They can be open and honest with each other and feel comfortable sharing their thoughts, feelings, and desires.

Both partners should pursue their interests and hobbies without compromising or sacrificing for the sake of the relationship. There’s no need to agree on everything – in fact, it’s healthy to have some separate interests – but overall, both partners should feel like they’re able to be true to themselves within the relationship.

Lots of good communication

In a healthy marriage, partners can communicate effectively. It means expressing needs and wants and listening and responding to what the other person is saying. There are mutual respect’s opinions, even if there are disagreements. Couples in a healthy marriage feel comfortable communicating with each other about both the good and the bad.

Good sex life

A good sex life can be a major sign of a healthy marriage. A lack of sexual activity can be an early warning sign that something is wrong in the relationship. Often, couples who have a good sex life are more connected emotionally and physically. They are also more likely to trust each other and communicate openly.

Trust in each other

In any relationship, trust is essential. Without trust, there is no foundation for the relationship to grow. In a marriage, trust is even more important. Trusting your spouse means you feel confident in their ability to support you emotionally and financially. It also means that you feel safe sharing your innermost thoughts and feelings with them.

When you trust your spouse, you know they have your best interests. You feel comfortable being yourselves around each other and sharing your hopes, dreams, and fears. Openness and honesty in your relationship allow you to be vulnerable with each other. This vulnerable honesty creates a deeper level of intimacy in your marriage.

When you trust each other, you can be more forgiving when mistakes are made. You know that everyone makes mistakes and that nobody is perfect. You also understand that your spouse is human and capable of making mistakes like anyone else. If they make a mistake, you are more likely to forgive them because you know they are sorry and will try not to make the same mistake again.

Trust is one of the most important foundations of a healthy marriage. If you want your marriage to thrive, build trust in each other.

A successful, strong marriage takes work, but with communication, trust, respect, vulnerability, and affection as its core components, you can together create a partnership that will be long-lasting.

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Obesity linked to macular degeneration

Immune cells are also activated when the body is exposed to stressors such as excess fat in obesity, making being overweight the number one non-genetic risk factor for developing AMD, after smoking.

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A Canadian study published in the prestigious journal Science elucidates a new molecular mechanism that may cause age-related macular degeneration (AMD).

The research at Hôpital Maisonneuve-Rosement, in Montreal, shows how life stressors such as obesity reprogram immune system cells and make them destructive to the eye as it ages.

“We wanted to know why some people with a genetic predisposition develop AMD while others are spared,” said Université de Montréal ophtalmology professor Przemyslaw (Mike) Sapieha, who led the study by his postdoctoral fellow Dr. Masayuki Hata.

“Although considerable effort has been invested in understanding the genes responsible for AMD, variations and mutations in susceptibility genes only increase the risk of developing the disease, but do not cause it,” Sapieha explained.

“This observation suggests that we must gain a better understanding of how other factors such as environment and lifestyle contribute to disease development.”

AMD is a major cause of irreversible blindness worldwide and affected approximately 196 million people in 2020. It comes in two forms:

  • dry AMD, characterized by the accumulation of fatty deposits at the back of the eye and the death of nerve cells in the eye,
  • and wet AMD, which is characterized by diseased blood vessels that develop in the most sensitive part of the sight-generating tissue, called the macula.

Contact with pathogens

It is already known that the immune system in the eye of a person with AMD becomes dysregulated and aggressive. Normally, immune cells keep the eye healthy, but contact with pathogens such as bacteria and viruses can make them go awry.

At the same time, immune cells are also activated when the body is exposed to stressors such as excess fat in obesity, making being overweight the number one non-genetic risk factor for developing AMD, after smoking.

In their study, Sapieha and Hata used obesity as a model to accelerate and exaggerate the stressors experienced by the body throughout life.

They found that transient obesity or a history of obesity leads to persistent changes in the DNA architecture within immune cells, making them more susceptible to producing inflammatory molecules.

“Our findings provide important information about the biology of the immune cells that cause AMD and will allow for the development of more tailored treatments in the future,” said Hata, now an ophthalmology professor at Kyoto University, in Japan.

The researchers hope their discovery will lead other scientists to broaden their interest beyond obesity-related diseases to other diseases characterized by increased neuroinflammation, including Alzheimer’s disease and multiple sclerosis.

About this study

“Past history of obesity triggers persistent epigenetic changes in innate immunity and exacerbates neuroinflammation,” by Mike Sapieha and Masayuki Hata, was published in Science.

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