Jared Berberabe

Adding a vaccine additive called an adjuvant to a vaccination enhances the body’s response to the vaccine, and may offer possibilities for a universal flu vaccine, according to an Emory Vaccine Center study.

Investigators found that both rookie and veteran elements of the immune system responded much more efficiently to the presence of the virus when the adjuvant was added.

“We saw that an adjuvant makes it possible to efficiently engage both memory and naive B cells, expanding the repertoire of the antibody immune response to influenza,” said Ali Ellebedy, PhD, an author of the study.

Proceedings of the National Academy of Sciences

, consisted of 50 healthy young adults who all had been previously exposed to various flu viruses and vaccines. Two doses of the adjuvant AS03 to the H5N1 avian influenza virus vaccine were applied to the group, and the results were compared with those from a non-adjuvanted vaccine.

The first dosage affected pre-existing memory B cells and directed cross-reactive antibodies to attack the virus stem. The second dosage affected strain-specific naïve B cells and encouraged antibodies to attack the virus head. Together, both pre-existing memory B cells and naïve B cells contributed to a more efficient immune response.

Previous research had noted that, faced with an unfamiliar flu virus, the immune system would produce antibodies that could neutralize a much wider range of viruses. These antibodies skewed towards the “stem” of the viral hemagglutinin protein, as opposed to the “head,” as the stem does not mutate much and could still be recognized by the antibodies.

The adjuvant trial demonstrates that an efficient immune response is tied to the recognition of a flu virus’s stem. If the immune system recognizes this but not the head, it can still launch antibodies towards the virus and negate it.

Such results open up new avenues for the development of a universal flu vaccine. But vaccine designers are already considering how to use adjuvants to optimize the immune responses against severe acute respiratory syndrome coronavirus 2 in order to overcome the body’s unfamiliarity with the virus. A vaccine that could induce a strong response from both memory and naïve B cells has the potential to be a strong alternative to other developmental mRNA-based vaccines.

As such, the adjuvant AS03 will be made available for COVID-19 vaccine trials, according to its manufacturer, GlaxoSmithKline.

Ellebedy AH, Nachbagauer R, Jackson KJL, et al. Adjuvanted H5N1 influenza vaccine enhances both cross-reactive memory B cell and strain-specific naïve B cell responses in humans. 

Proceedings of the National Academy of Sciences of the United States of America

Eastman, Q. Vaccine additives can enhance immune flexibility—implications for flu and SARS-CoV-2. News Release. Emory University

 Published July 13, 2020. Accessed July 20, 2020. 

https://news.emory.edu/stories/2020/07/H5N1_adjuvants_ahmed/index.html

Articles

By adding an adjuvant to an existing vaccine treatment, it’s possible to optimize the body’s response to the presence of a virus. 

Vaccine Additive Strengthens Immune Response, Offers Possibilities for Universal Flu Vaccine

 determined an association between higher mortality rates and extremes of sleep duration in adults with type 2 diabetes.

The study was based on data from the United States and was conducted by a team of Chinese investigators hoping to determine to what extent the effects of sleep duration interacted with diabetes. The team also aimed to examine how sleep duration related to all-cause and cause-specific mortality in individuals with this disease.

A total of 273,029 individuals participated in the study; 248,817 individuals without diabetes and 24,212 with type 2 diabetes. The individuals were part of the National Health Interview Survey conducted from 2004 and 2013.

In the survey, individuals were asked “on average how long do you sleep each day?” on a 5 to 10 hour per day scale. From this data, the team of investigators employed a Cox proportional hazards regression model, which adjusted for demographics, body mass index (BMI), lifestyle behaviors and clinical variables, to determine the relation between higher death rates and differences in the number of hours slept.

Mortality numbers were determined out of 10,000 person-years. For both groups with and without diabetes, the reference number of hours was 7.

The investigators used individuals without diabetes who slept 7 hours as the reference comparison group. The model found that absolute mortality rate in adults tended to be higher in those with diabetes and those who demonstrated extremes of sleep duration—extremes being sleeping less than 5 hours per day, or more than 10 hours per day—when compared with the reference group. At less than 5 hours, the mortality rate was 215 per 10,000 person-years; at more than 10 hours, the rate was 364 per 10,000 person-years.

A similar but more subdued pattern emerged in the other group, with individuals without diabetes in the 7-hour reference group having a mortality rate of 78 per 10,000 person-years. Those without diabetes who slept for less than 5 hours had a death rate of 122; those who slept more than 10 had a rate of 256.

The new study found an association between sleep duration, type 2 diabetes, and cause-specific mortality. Cancer mortality was 41% higher in individuals with diabetes who slept less than 5 hours per day, and 59% in those who slept more than 10. Cardiovascular disease (CVD) mortality was statistically higher for 10-hour sleepers, at a 74% increased risk, when compared with 7 hours of sleep. The longest sleep groups further demonstrated an increased risk of death by stroke or Alzheimer disease.

Previous research, the authors noted, already demonstrated that extreme levels of sleep duration could have significantly negative effects on an individual, and that poor sleep could result in a 40% slower glucose clearance rate for the body. For individuals with diabetes, this could prove fatal, as a slower rate could aggravate the status of insulin resistance, obesity, and high blood pressure.

The team noted, however, that the data gathered was still based on self-reported information, without use of objective measurements. The study also did not include non-fatal events that may have contributed variables to the risk of death. Additionally, the study lacked data on other factors, such as the number and age of young children, and the kind of employment, medications, and mental illness, that could have contributed to the quality of sleep, and therefore the hours spent sleeping.

Nevertheless, the team emphasized the importance of having a sufficient and healthy sleep duration. They recommend that both individuals with and without type 2 diabetes get 6 to 8 hours of sleep per night.

In reference to their findings regarding higher rates of death in individuals with type 2 diabetes, the team posited the possibility of including sleep interventions in present diabetes treatments. “These patients may require greater medical attention that targets sleep and lifestyle to reduce the risks of adverse health outcomes,” the investigators concluded.

Wang Y, Huang W, O’Neil Adrienne, et al. Association between sleep duration and mortality risk among adults with type 2 diabetes: a prospective cohort study. 

https://doi.org/10.1007/s00125-020-05214-4

Study finds link between too much or too little sleep and increased death rates in patients with or without diabetes. News Release. 

. Accessed July 20, 2020. Published July 16, 2020. 

https://www.eurekalert.org/pub_releases/2020-07/d-sfl071420.php

Individuals with type 2 diabetes who exhibit extreme sleep duration hours may have a higher risk of death than individuals without diabetes. 

Study Determines Association Between Mortality Rates and Sleep Duration in Adults with Type 2 Diabetes

Two vaccine candidates from Pfizer Inc and BioNTech SE being developed to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) received Fast Track designation from the FDA, which will allow the companies to begin phase 2b/3 safety and efficacy studies for the vaccines.

The 2 candidates, BNT162b1 and BNT162b2, are part of the join BNT162 program that was being evaluated in ongoing phase 1/2 clinical studies in both the United States and Germany. They were part of a group of 4 candidates and are considered the most advanced in the program.

Each candidate in the program represented a unique combination of messenger RNA (mRNA) and target antigen. BNT162b1 and BNT162b2, both nucleoside-modified RNAs, are encoded respectively with an optimized SARS-CoV-2 receptor-binding domain (RBD) antigen and a SARS-CoV-2 full-length spike protein antigen.

The Fast Track designation was based on preliminary data from phase 1/2 studies released in the United States on July 1, 2020 for BNT162b1, with the German trial data expected to release soon. Pfizer and BioNTech hope to start phase 2b/3 trials later in July with an anticipated enrollment of 30,000 subjects. Assuming the current studies are successful, and that the candidates receive regulatory approval, both companies hope to develop 100 million doses for the novel coronavirus 2019 (COVID-19) by the end of 2020, and possibly 1.2 billion doses or more at the end of 2021.

“The FDA’s decision to grant these 2 COVID-19 vaccine candidates Fast Track designation signifies an important milestone in the efforts to develop a safe and effective vaccine against SARS-CoV-2,” Peter Honig, senior vice president, global regulatory affairs, Pfizer, said in a statement. “We look forward to continue working closely with the FDA throughout the clinical development of this program, Project Lightspeed, to evaluate the safety and efficacy of these vaccine candidates.”

Pfizer and BioNTech Granted FDA Fast Track Designation for Two Investigational mRNA-based Vaccine Candidates Against SARS-CoV-2. News Release Pfizer; July 13, 2020. Accessed July 15, 2020. 

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-granted-fda-fast-track-designation-two

Pfizer and BioNTech SE announced that 2 of its most successful vaccine candidates received Fast Track designation from the FDA, opening the avenue for speedy development.

FDA Grants Fast Track Designation for 2 MRNA-Based COVID-19 Vaccine Candidates

ViiV Healthcare announced new data from the HIV Prevention Trials network (HPTN) 083 study at the 23rd International AIDS Conference (AIDS 2020) that demonstrated the superiority of investigational long-acting injectable formulation of cabotegravir compared with daily oral pre-exposure prophylaxis (PrEP) tablets in preventing HIV acquisition.

“This advancement has the potential to be a game-changer for HIV prevention, offering an option with very high rates of effectiveness and the convenience of reduced dosing from daily to just 6 times per year,” said Kimberly Smith, MD, MPH, and head of research and development at ViiV Healthcare. “We are thrilled with the results not only because of the high effectiveness of cabotegravir but also because this study adequately represents some of the populations most disproportionately impacted by HIV— black [men who have sex with men (MSM)] in the US, young MSM globally, and transgender women.”

The HPTN 083 study was a phase 2b/3 randomized, multicenter, double-blind, clinical trial that sought to evaluate the safety and effectiveness of cabotegravir when compared with daily oral emtricitabine/tenofovir disoproxil fumarate 200 mg and 300 mg (FTC/TDF) tablets normally used in HIV prevention. Fifty two total documented cases of HIV were observed, with 13 being treated with long-acting cabotegravir and 39 with daily oral FTC/TDF.

The study consisted of HIV-negative men and transgender women who have sex with men, all of whom were considered at higher risk for HIV. Two-thirds were under the age of 30, with a median age of 26, and 12% of the total were transgender women, whereas half were identified as Black or African American.

Though there were higher levels of adherence to oral therapy, based on data from 87% of the participants that detected levels of tenofovir, long-acting cabotegravir nevertheless translated lower HIV incidence rates. The cabotegravir group achieved a 0.41% rate of infection, compared with 1.22% in the FTC/TDF group.

Consequently, in terms of effectiveness, cabotegravir was 66% more effective than FTC/TDF tablets were in preventing HIV in the study population.

Although both treatments were well-tolerated during the study, reactions to the injection site, including pain or tenderness, was mentioned by 80% of participants in the cabotegravir group. Other reactions included pyrexia and hypertension. Nausea was more common in the FTC/TDF group. There was a 2.2% rate of discontinuation of cabotegravir injection due to this, and no discontinuations in the FTC/TDF group.

An additional study is being conducted in sexually active women, as part of the HIV Prevention Trials Network 084, with more than 3000 sexually active women across 7 African countries presently enrolled.

Cabotegravir has yet to be approved by regulatory authorities, but many are hopeful. “Medicines that help prevent new HIV incidence are essential to our ongoing global fight to end the HIV epidemic,” said Myron S. Cohen, MD, co-principal investigator of the HPTN and the Yeargan-Bate distinguished professor of medicine, microbiology and immunology and epidemiology at the University of North Carolina at Chapel Hill.

“It’s exciting to discover that with injectable, long-acting cabotegravir, we now have compelling clinical evidence of another effective PrEP option that could play a critical role in helping to reduce HIV transmission that will ultimately save lives,” Cohen said.

ViiV Healthcare Announces Superior Efficacy of Investigational, Long-Acting Injectable Formulation of Cabotegravir Dosed Every Two Months Over Daily oral PrEP. News Release. Businesswire; July 7, 2020. Accessed July 8, 2020. 

https://www.businesswire.com/news/home/20200707005511/en/ViiV-Healthcare-Announces-Superior-Efficacy-Investigational-Long-Acting

The data from a new study has shown that investigational, long-acting injectable cabotegravir boasted a 66% higher efficacy than daily oral pills in preventing HIV-1.