Day: September 1, 2021

MMR and Tdap Vaccines May Confer Some COVID Protection

Source: Pixabay CC0

Mounting evidence shows that the Measles-Mumps-Rubella (MMR) and Tetanus-Diphtheria-Pertussis (Tdap) vaccines confer limited protection against COVID.

The MMR vaccine, given during early childhood, and Tdap vaccine, given every 10 years, elicit protective responses against the diseases they are designed for. It’s possible that they also elicit cross-reactive memory T cells that can respond to antigens that are present in other pathogens — including the viral antigens in SARS-CoV-2. The idea is that pre-existing memory T cells generated by prior MMR or Tdap vaccination and activated by SARS-CoV-2 infection give the immune system a head start in responding to SARS-CoV-2, lowering the risk of severe COVID.

To find out if the MMR and Tdap vaccines provide additional protection against COVID, researchers at Brigham and Women’s Hospital performed laboratory-based analyses with new techniques to detect and characterise T cell responses to antigens. They applied these techniques to measure T cell responses isolated from the blood of COVID convalescent patients and patients vaccinated against COVID to antigens from SARS-CoV-2 and the MMR and Tdap vaccines. They also leveraged a large, well-annotated cohort of COVID patients and found that prior MMR or Tdap vaccination was associated with decreased disease severity. Their results are published in Med.

“Our Cleveland Clinic colleagues observed an association where individuals with COVID who had either MMR or Tdap vaccines had a much lower frequency of going to the intensive care unit or dying,” said co-author Andrew Lichtman, MD, PhD, an immunologist and senior investigator in the Brigham’s Department of Pathology and professor of Pathology at Harvard Medical School. “Although previous smaller studies suggested a similar link, our in-depth epidemiological analyses, together with our basic research results, suggest that these commonly given vaccines may protect against severe disease.”

“During the COVID pandemic, we know that there was a marked decline in routine vaccinations for children and adolescents,” said corresponding author Tanya Mayadas, PhD, a senior scientist in the Brigham’s Department of Pathology and professor of Pathology at Harvard Medical School. “Our findings emphasise the importance of routine vaccination for children and adults. We know vaccines protect against devastating diseases, and we’re now seeing growing evidence that some of them provide a degree of protection against severe COVID disease.”

An unexpected observation jumpstarted the investigation. Prof Mayadas, her postdoctoral fellow Vijaya Mysore, PhD, and colleagues noted in lab experiments with COVID convalescent blood that whenever they observed a heightened T cell response to SARS-CoV-2 proteins, they also saw a heightened response to proteins from MMR and Tdap, which were controls. This was seen in both COVID convalescent and uninfected individuals vaccinated against SARS-CoV-2.

In a subsequent analysis, Prof Mayadas and colleagues teamed up with researchers at Cleveland Clinic to examine the epidemiological evidence. The Cleveland Clinic team performed a retrospective cohort study using data from more than 75 000 patients seen at the Cleveland Clinic Health System in Ohio or Florida who had tested positive for COVID between March 8, 2020, and March 31, 2021. A statistical analysis found that patients who had previously been vaccinated for MMR had a 38 percent decrease in hospitalisation and a 32 percent decrease in ICU admission/death. Patients previously vaccinated for Tdap had 23 percent and 20 percent decreased rates, for these outcomes, respectively.

“Beyond learning about the potential benefits of the MMR and Tdap vaccines in the context of COVID, this study provides a blueprint for accelerating research,” said co-author Lara Jehi, MD, MHCDS, Chief Research Information Officer of the Cleveland Clinic Health System. “Biomedical hypotheses generated in the laboratory can be explored through robust clinical and epidemiological research in well-curated, real-world data such as the Cleveland Clinic COVID Registry. Knowledge learned through this collaboration is much more than the sum of our individual parts.”

The authors note that epidemiological observations strengthen their lab findings, more work is needed to find a causal association between the MMR and Tdap vaccinations and severity of COVID disease.

“With regards to COVID vaccines, our findings predict that although MMR and Tdap are not a substitute for COVID vaccines they may afford greater and more durable protection, possibly against emerging spike variants than the COVID vaccine alone,” said Prof Mayadas. “And in areas where the COVID vaccines are not available, they could protect infected individuals from developing severe disease.”

Source: Brigham and Women’s Hospital

How Blood Vessels Change Permeability

Source: Wikimedia CC0

Researchers have made steps toward understanding how blood vessels change permeability, and how they might intervene to restore blood vessel integrity during sepsis, trauma or other conditions.

Sepsis occurs when a patient’s over-activated immune system harms their own tissues. As a result, blood vessels can become ‘leaky’ and can’t adequately supply major organs. The condition is notoriously difficult to treat, and there are no drugs that help stabilize the cell barrier that lines blood vessels.

A protein, HSP27, was previously found by researchers at University of California San Diego to be involved in regulating blood vessel leakage. To help break down or build up blood vessel barrier, cells add and remove chemical tags on HSP27.

The study, reported in Science Signaling, provides new potential targets for the development of drugs that shore up blood vessel barriers, preventing fluid loss.

“This new information will help us home in on the root cause of leaky blood vessels, rather than taking a broad strokes approach that may have many off-target effects,” said senior author JoAnn Trejo, Ph.D., professor of pharmacology and assistant vice chancellor of the Office of Health Sciences Faculty Affairs at UC San Diego School of Medicine.

Blood vessel barriers need to be permeable enough to allow immune cells to squeeze out to reach the site of an infection, for example, but not so much that the situation becomes life-threatening. HSP27 binds to proteins that help form the cell’s “skeleton.” Prof Trejo and colleagues suspect that’s how HSP27 affects blood vessel permeability: by reinforcing the skeleton of cells that maintain the barrier.

Prof Trejo has long studied G-protein-coupled receptors (GPCRs), proteins that are embedded in cell membranes and act as signal transducers for cells. About a third of all therapeutic drugs on the market work because they influence GPCR signals.

In their latest study, the team found that during inflammation, GPCRs tell enzymes called kinases to add chemical (phosphate) tags to HSP27. The tags perturb HSP27’s structure in a way that disrupts blood vessel barriers. When HSP27 reassembles, the barriers recover. The researchers validated their lab studies in mice, where they found that inhibiting HSP27 increases blood vessel leakage.

One problem in targeting GPCRs to treat a disease is that most act as master regulators, influencing many different cell functions. Inhibiting one GPCR may therefore have many unintended consequences. By aiming not at the master GPCR but at individual targets upon which it acts, such as HSP27, Trejo’s team is hoping to enable the development of blood vessel barrier-stabilising drugs that have greater precision and fewer side effects.

“It’s become apparent that you can develop different molecules that can bind to receptor and ‘bias’ them — make them signal in a very specific way to some pathways but not others,” Prof Trejo said. “It’s what we call biased agonism, and it’s a huge advantage for drug development. It means we can develop not just an on/off switch, but a drug that can switch a receptor ‘off’ or eight different types of ‘on.’ We want to be able to tweak which pathways are on and not touch others.”

The team plans to explore additional cell signaling pathways that helps blood vessels build resistance to injury and inflammation.

Source: UC San Diego

Traitorous Immune Cells Explain Why the Elderly Feel the Cold

Photo by Adam Birkett on Unsplash

In a new study, Yale researchers found that the immune cells within fat that are designed to burn calories to protect us from cold temperatures start to turn against us as we age, making the elderly more vulnerable to the cold.

The study, published in Cell Metabolism, found that the fat tissue of older mice loses the immune cell group 2 innate lymphoid cells (ILC2) which restore body heat in cold temperatures. However, trying to stimulate production of new ILC2 cells in aging mice actually makes them more prone to cold-induced death, showing how difficult it is to solve aging-related problems.

“What is good for you when you are young, can become detrimental to you as you age,” said Vishwa Deep Dixit, the Waldemar Von Zedtwitz Professor of Comparative Medicine and of Immunobiology and co-corresponding author of the study.

Prof Dixit and former colleague Emily Goldberg, now an assistant professor at UCSF, were curious about why there are immune cells in fat tissue, as they are usually concentrated in pathogen-exposed areas like nasal passages, lungs, and skin. When they sequenced genes from cells of old and young mice they found that older animals lacked ILC2 cells, a deficit which limited their ability to burn fat in cold conditions.

When they introduced a molecule that boosts the production of ILC2 in aging mice, the immune system cells were restored but the mice were surprisingly even less tolerant of cold temperatures.

“The simple assumption is that if we restore something that is lost, then we are also going to restore life back to normal,” Dixit said. “But that is not what happened. Instead of expanding healthy cells of youth, the growth factor ended up multiplying the bad ILC2 cells that remained in fat of old mice.”

However, when ILC2 cells were taken from younger mice and transplanted into older mice, the older animals’ cold tolerance was restored.

“Immune cells play a role beyond just pathogen defense and help maintain normal metabolic functions of life,” Dixit said. “With age, the immune system has already changed and we need to be careful how we manipulate it to restore the health of the elderly.”

Source: SciTech Daily

August Poll Results; 18-34s Upbeat on Vaccines

Photo by Mufid Majnun on Unsplash

To date, nearly 12 600 000 vaccinations have been administered in South Africa, with 23.66% of the adult population now fully vaccinated. Quicknews’ August poll revealed that 44% of site visitors felt that the government’s COVID vaccine rollout was “Acceptable”, while 51% felt it was either “Poor” or “Very Poor”. Only 5% rated it “Good” or “Very Good”.

The Department of Health’s COVID-19 and Vaccine Social Listening Report finds that the demand for vaccination had increased, with around 250 000 daily jabs, fuelled by a surge by the recent eligibility of the 18 – 34 age group. The report highlights include:

  • Social media conversations are more positive about the vaccine rollout with improved services, such as free transport and pop-up vaccination sites. Barriers to vaccination seem now to be more of an issue than vaccine hesitancy. It is noticeable that most anti-vax videos originated from other countries (especially the US), while most pro-vax are local (eg celebrating being vaccinated).
  • While vaccination is met with eagerness and discussion among the 18 – 34 age group, they also still appear to be the most vaccine-resistant age group, believing themselves to be healthy and not needing a vaccine. Discussion over whether vaccines should be mandatory is ongoing, eg to go to concerts, with some disinformation suggesting that it is already happening, and a sign of control by the state.
  • There has been increasing media coverage supportive to vaccines. The Department of Health’s vaccine demand acceleration plan has been met positively, as well as favourable coverage of the FDA’s full approval of the Pfizer vaccine. 
  • However, there are some negative views of the government’s vaccine prioritisation, and is seen as neglecting basic services such as sanitation and public transport. 
  • A WhatsApp survey run by suggests that 90% of 4,000 people who had been vaccinated are willing to encourage others to do so. People reportedly have more rational concerns about vaccines (efficacy, side effects, developed so quickly, reports of deaths) and not the wilder conspiracy theories (eg tracking devices, depopulation).
  • Disinformation and problematic statements such as those from Rev Kenneth Meshoe vaccine-resistant statements and support for anti-vaxxers Dr Susan Vosloo and Prof Tim Noakes have undermined vaccine trust.
  • There is some debate over preferences over currently available vaccines or those that may be available later, eg Astra Zeneca, Sinovac. Confusion on reports that J&J second dose might be required and other booster shots.
  • The report notes some anti-vaccination sentiment in the Muslim community, with messages circulated that vaccines are haram (forbidden by Sharia law), though most Muslim authorities produce responsible evidence-based views.

Source: SA Coronavirus Portal

Suspensions of Top Health Officials are Imminent

Photo by Bill Oxford on Unsplash

An article by the Daily Maverick reveals that a wave of suspensions in the Department of Health are impending as a result of the investigation into the Digital Vibes contract, which prompted the resignation of Dr Zweli Mkhize.

Minister of Health Dr Joe Phaahla said that he received a letter from the Special Investigations Unit (SIU) which he would have to act on. 

Dr Phaahla said that “in the next few days and weeks there will unfortunately be some action and that will have some impact also on our capacity as a department”, adding that “when wrong things have happened and investigations have led to findings, then people have to be held answerable”.

However, Dr Phaahla said it was regrettable since “it will have an impact on our capacity, because from what I have seen, a number of people will have to be on suspension, pending charges.” He said it would be difficult for the vaccination programme as management staff were already stretched thin, but “it’s a consequence which must follow”. 

Drs Buthelezi and Pillay denied any knowledge of suspension, though the Daily Maverick has found out that referral for disciplinary action have been sent to the presidency.

The details of the SIU’s investigation have not been made public yet, although the Daily Maverick was able to tease out some details from an affidavit to set aside the Digital Vibes contract and to seeks to reclaim up to R150 million that was paid for the contract.

The affidavit further reveals that Dr Mkhize allegedly pressured the previous Director-General, Precious Matsoso, to employ Tahera Mather to be contracted for communication.

Precious Matsotso was replaced after an unblemished ten years by Dr Anban Pillay, who had been Deputy DG. Dr Pillay then became the active facilitator for the Digital Vibes contract, the affidavit suggests — a matter in which the DIU has also referred to the National Prosecuting Authority.

The current DG, Dr Sandile Buthelezi, who replaced Dr Pillay, is also noted as approving payments to Digital Vibes, though the DIU states it is not seeking any relief against him other than setting aside of relevant agreements.

The situation still has a way to run, with disciplinary inquiries, the Special Tribunal hearing and NPA investigations all ongoing. 

However, the Daily Maverick warns that it is clear that this critical government department is in “freefall” and will not have the capacity to deal with South Africa’s health challenges in the months and years to come.

Source: Daily Maverick

J&J HIV Vaccine Fails in Local Trials

HIV invading a human cell
HIV invading a human cell: Credit NIH

Johnson & Johnson and its partners announced preliminary results showing their HIV vaccine trial failed to provide sufficient protection against HIV infection in a population of young women in sub-Saharan Africa.

The vaccine had a favourable safety profile with no serious adverse events.
The Phase 2b HIV vaccine clinical trial was known as the Imbokodo study (also known as HVTN 705/HPX2008), which will now be discontinued. Further analysis of the Imbokodo study is ongoing, and the study has provided enough data to progress with key immunological correlates research.

“The high incidence of HIV among young women in sub-Saharan Africa reminds us that, despite great progress made in treatment and prevention, HIV remains a major health challenge for the region,” said Professor Glenda Gray, President and Chief Executive Officer, South African Medical Research Council (SAMRC) and Imbokodo’s Protocol Chair. “This underscores the need to apply the knowledge that will be gained from this trial to continue to advance the pursuit of a global HIV vaccine.”A parallel, ongoing Phase 3 Mosaico study (HVTN 706/HPX3002) with men who have sex with men and transgender individuals in Europe and Americas will continue due to the different HIV strains that are circulating in the trial areas and the different HIV vaccine regimen.
The HIV regimen consisted of an adenovirus vector containing four mosaic immunogens (Ad26.Mos4.HIV) at four vaccination visits over one year. The Imbokodo regimen contains a soluble protein component (Clade C gp140, adjuvanted with aluminum phosphate) which is administered at vaccination visits three and four. The ongoing Phase 3 Mosaico study is testing a different investigational vaccine regimen that involves the administration of a mosaic-based mixture of soluble proteins (Clade C/Mosaic gp140) at vaccination visits three and four.

Imbokodo participants had four vaccination visits over one year, with the primary endpoint based on new HIV infections through month 24. These data found that 63 of 1109 placebo arm participants compared to 51 of 1079 vaccine arm participants. This analysis demonstrated a vaccine efficacy point estimate of 25.2% (95% confidence interval of -10.5% to 49.3%).

HIV is prevalent in Sub-Saharan Africa, where women and girls accounted for 63 percent of all new HIV infections in 2020. The study enrolled roughly 2600 young women across Malawi, Mozambique, South Africa, Zambia and Zimbabwe. Researchers ensured that any HIV-infected participants in Imbokodo were referred to high-quality HIV treatment and care services. 

Source: PR Newswire