Tag: BCG vaccine

Categories : Neurodegenerative Diseases VaccinesTags :

Could the BCG Vaccine Reduce Alzheimer’s Risk?

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Photo by Mari Lezhava on Unsplash

The Bacillus Calmette-Guérin (BCG) for tuberculosis vaccine has a number additional beneficial effects, and is currently a recommended therapy for non–muscle-invasive bladder cancer. In a new study published in JAMA Network Open, treatment with the BCG vaccine was associated with a reduced risk of Alzheimer’s disease and related dementias.

Although previous research has suggested a link between the BCG vaccine and a lower risk of dementia, studies were limited by size, study design, or analytical methods. To conduct a more robust study, researchers followed 6467 individuals for up to 15 years after they were diagnosed with non–muscle-invasive bladder cancer.

The group included 3388 patients who underwent BCG vaccine treatment and 3079 who served as controls, matched by factors such as age, sex, and medical co-morbidities.

During follow-up, 202 patients in the BCG vaccine group and 262 in the control group developed Alzheimer’s disease and related dementias. The incidence was 8.8 per 1000 person-years and 12.1 per 1000 person-years in the respective groups.

Analyses revealed that treatment with the BCG vaccine was associated with a 20% lower risk of Alzheimer’s disease and related dementias. The protective association was greater in patients aged 70 years or older. Additionally, during follow-up, 751 patients in the BCG vaccine group and 973 in the control group died. Thus, treatment with BCG vaccine was associated with a 25% lower risk of death.

Study leader Marc Weinberg, MD, Ph.D., an Instructor in Psychiatry at MGH, said: “A vaccine like BCG, if proven effective, is a perfect example of a cost-effective, population-health–based solution to a devastating illness like Alzheimer’s disease. We are shifting our focus towards studying the potential benefits of BCG vaccination of older adults in Alzheimer’s disease–related clinical trials.”

If a causal link is found, it will be important to understand the mechanisms involved. Weinberg and his colleagues note that the BCG vaccine’s effects on the immune system may play a role.

Source: Massachusetts General Hospital

Categories : Paediatrics VaccinesTags :

Infant BCG Vaccination Only Protects up to Five Years of Age

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Syringe withdrawing from vaccine vial
Photo by Mufid Majnun

A study has found that the Bacillus Calmette-Guérin (BCG) vaccine, when administered in infancy, only protects against tuberculosis (TB) in children under five years of age. The findings, published in The Lancet Global Health, showed that the vaccine provided no protection among adolescents or adults in the study.

Despite the age and widespread use of the BCG vaccine, debate continues on how effective it is in preventing TB, and the duration of immunity after it is administered in infancy. And as experts study and propose new TB vaccines to supplement the BCG vaccine, an important consideration is the age at which these new vaccines should be administered to high-risk populations.

Gathered from 20 years of recent studies, this analysis provides new insight and clarity on these issues.

These results suggest that protectiveness from the BCG vaccine may begin to wane as children get older and, thus, children over 10 years old and adults should receive a booster BCG vaccine for immunity against TB beyond childhood. Unfortunately, a BCG booster has limited efficacy, so new vaccines are needed.

“Unlike many of the mRNA COVID vaccines, which we know are highly effective, there is widespread debate on the BCG vaccine’s effectiveness and duration of protection, as well as whether the vaccine only works in selective settings,” explained study lead author Leonardo Martinez, assistant professor of epidemiology at Boston University School of Public Health. “Our findings indicate that BCG vaccination is effective at preventing tuberculosis in young children. Since tuberculosis in children is a highly debilitating and severe disease, BCG vaccination should continue to be used.”

However, since the results show that the vaccine was ineffective in adolescents and adults, “boosting immunoprotection is needed for older populations,” Asst Prof Martinez said. “Novel vaccines are urgently needed to supplement BCG vaccination in high-burden settings.”

Most studies on this subject were done over 50 years ago, with varying results, and primarily in settings with a relatively low burden of the disease. This new analysis presents data over the past 10 years, from high-burden settings in 17 countries, including South Africa, China, Vietnam, Indonesia, Uganda, The Gambia, and Brazil.

For the study, Asst Prof Martinez and colleagues analysed individual-level data from 26 longitudinal studies that included nearly 70 000 participants exposed to TB from 1998 to 2018. The researchers examined the impact of BCG vaccination for all TB disease, as well as specifically for pulmonary and extrapulmonary TB. The analysis examined variability across the studies, including the use of skin and blood TB infection tests, and accounted for potentially confounding factors such as HIV, exposure status, and history of prior TB, amongst others.

Among all children under 5 years old, BCG vaccination was 37% effective. The researchers did not find conclusive evidence that the vaccine was protective among children over 10 or among adults. When focusing only on pulmonary TB, BCG vaccination was 19% effective, however this effect was also only among young children.

The researchers stress that substantial investment in TB vaccine development is critical to controlling global TB.

“We urgently need vaccines that are effective against tuberculosis in adults,” said study co-author C. Robert Horsburgh, professor of epidemiology. “There are a number of promising TB vaccine candidates under study and we hope that one or more of them will prove effective.”

Source: Boston University

Categories : VaccinesTags :

New Tuberculosis Vaccine Passes Safety Hurdle in SA Trial

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Tuberculosis bacteria
Tuberculosis bacteria. Credit: CDC

The only vaccine currently available against tuberculosis, Bacillus Calmette Guérin (BCG), is not equally effective against all types of tuberculosis. A clinical trial in South Africa has now shown that the new vaccine candidate VPM1002, decades in development, is equally safe for newborns with and without HIV exposure and has fewer side effects compared to BCG.

First used 100 years ago, the BCG vaccine against the disease contains attenuated pathogens of cattle tuberculosis. “We know that BCG can prevent so-called tuberculous meningitis and miliary tuberculosis in infants with a 75 to 86 percent effectiveness rate. But this is not the case for the most common form of the disease, pulmonary tuberculosis, in all age groups. Here, BCG is only insufficiently effective,” explained Max Planck researcher Stefan H.E. Kaufmann, who developed the vaccine with his team.

Since the 1990s, the infection biologist and his team have been working on an improved next-generation vaccine, called VPM1002. To achieve this, the researchers genetically modified the attenuated BCG vaccine strain so that immune cells can better recognise the pathogens. “We developed VPM1002 in no small part to combine increased safety with improved efficacy for immunocompromised children,” Kaufmann said.

Vaccine candidate VPM1002 is safe

The group of immunocompromised children includes, for example, HIV-exposed infants born to HIV-positive mothers. In a clinical trial in South Africa, researchers compared VPM1002 with BCG in HIV-exposed and non-HIV-exposed newborns. The study examined both the safety and the immunogenicity associated with the formation of immune cells and immunostimulatory proteins. The study, published in Lancet Infectious Diseases, concluded that VPM1002 is safe in both HIV-exposed and non-HIV-exposed newborns, has fewer side effects than BCG, and elicits a similar immune response.

In the randomised phase II double-blind study in South Africa, 416 eligible newborns were randomly selected and vaccinated before day 12 of life. 312 of them received VPM1002, and 104 received the BCG vaccine. As the study showed, VPM1002 triggered fewer vaccine-related adverse reactions than BCG. This was true for reactions occurring at the injection site, such as scarring and abscess formation, as well as enlargement of lymph nodes. This finding is important because local and regional reactions after vaccination are among the limitations of the BCG vaccine, Kaufmann points out.

Newborns with or without HIV exposure showed similar immunogenicity with both vaccines, though starting at six weeks of age, the BCG-triggered immune response was greater than in even younger infants.

Phase III study investigates protection

“Studies such as those described here examine a vaccine’s immunogenicity, but not its protection. For the latter, we have already developed a larger phase III clinical trial and have successfully enrolled mothers with their newborns to participate. Now the clock is ticking,” Kaufmann said. He expects initial results showing whether VPM1002 can provide comparable or better protection than existing BCG vaccines in about three years. In addition, VPM1002 vaccine is currently in two other phase III clinical trials in India for protection against tuberculosis, which expected to be completed in 2023 and 2024.

Source: Max-Planck-Gesellschaft

Categories : VaccinesTags :

BCG Vaccine Activates Immune System in Newborns

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Syringe
Source: Raghavendra V Konkathi on Unsplash

In the century since it was first used in humans, the Bacille Calmette-Guérin (BCG) vaccine against tuberculosis has become one of the world’s most widely used vaccines. Administered in countries with endemic TB, it has surprisingly been found to protect newborns and young infants against multiple bacterial and viral infections unrelated to TB. Some evidence even suggests that it can reduce severity of COVID. Now, a new study in Cell Reports sheds light on the mechanisms behind its extra protective effects.

Surprisingly little is known about how BCG exerts its many side benefits. To better understand its mechanism of action, researchers collected and comprehensively profile blood samples from newborns vaccinated with BCG, using a powerful ‘big data’ approach analysing lipid and metabolite biomarkers.

Their study found that the BCG vaccine induces specific changes in metabolites and lipids that correlate with innate immune system responses. The findings provide clues toward making other vaccines more effective in vulnerable populations with distinct immune systems, such as newborns.

First author Dr Joann Diray Arce and her colleagues started off with blood samples from low-birthweight newborns in Guinea Bissau who were enrolled in a randomised clinical trial to receive BCG either at birth or after a delay of six weeks. Blood samples were taken at four weeks for both groups (after BCG was given to the first group, and before it was given to the second group).

The researchers comprehensively profiled the impact of BCG immunisation on the newborns’ blood plasma. They found that BCG vaccines given at birth changed metabolite and lipid profiles in newborns’ blood plasma in a pattern distinct from those in the delayed-vaccine group. The changes were associated with changes in cytokine production, a key feature of innate immunity.

The researchers had parallel findings when they tested BCG in cord blood samples from a cohort of Boston newborns and samples from a separate study of newborns in The Gambia and Papua New Guinea.

“We now have some lipid and metabolic biomarkers of vaccine protection that we can test and manipulate in mouse models,” said Dr Arce. “We studied three different BCG formulations and showed that they converge on similar pathways of interest. Reshaping of the metabolome by BCG may contribute to the molecular mechanisms of a newborn’s immune response.”

“A growing number of studies show that BCG vaccine protects against unrelated infections,” said Ofer Levy, MD, PhD, the study’s senior investigator. “It’s critical that we learn from BCG to better understand how to protect newborns. BCG is an ‘old school’ vaccine – it’s made from a live, weakened germ – but live vaccines like BCG seem to activate the immune system in a very different way in early life, providing broad protection against a range of bacterial and viral infections. There’s much work ahead to better understand that and use that information to build better vaccines for infants.”

Source: Boston Children’s Hospital via News-Medical.Net

Categories : Diseases, Syndromes and Conditions VaccinesTags :

Boosting the BCG Vaccine by Blocking IL-10

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Vaccine injection
Image source: NCI on Unsplash

Briefly blocking interleukin-10 (IL-10) when administering the BCG vaccine for tuberculosis vastly improves long-term protection in mice, researchers reported in the Journal of Immunology. The finding, if it continues to hold true in nonhuman primates and clinical trials, has the potential to save millions of lives.

“We are very excited that we can reverse BCG’s waning effectiveness by combining it with a host-directed therapy into one dose, which makes it very practical for the clinic,” said senior author Joanne Turner, PhD.

The study builds on research showing the effect of IL-10 on TB, which normally helps dampen excessive inflammation during infection, but Dr Turner’s previous work showed that IL-10 overall actually drives infection.

The researchers combined the BCG vaccine with an antibody that blocks IL-10 activity for about one week. Since the antibody targets the host, not the pathogen, that makes it a “host-directed therapy.” They gave the mixture to mice in one shot, waited six weeks to ensure the IL-10 blocker was no longer present and the BCG protection had been generated, and then exposed the mice to TB. Those mice controlled TB infection for nearly a year, which is significant for mice with normal lifespans of about two years. In contrast, mice given only the BCG vaccine lost control of TB infection within two months and had significant inflammation and damage in the lungs. Notably, the mice given the vaccine/IL-10 blocker had higher levels of various long-term memory immune cells, which are critical for ongoing TB control.

“This shows that the early development of an immune response is key for controlling TB infection in the long run, and that IL-10 inhibits the development of that long-term immunity,” Dr Turner said. “But by briefly blocking IL-10 at the same time as giving the vaccine, it allows the vaccine and immune system to do their jobs, creating those long-lasting memory immune cells.”

The researchers plan to move to nonhuman primates and then human clinical trials if those are successful. The team is optimistic, especially since the BCG vaccine is already in widespread use and the IL-10 blocker is being tested against other diseases.

Source: Texas Biomedical Research Institute