A Cochrane review of all the evidence available from randomised controlled trials of COVID vaccines up to November 2021 has concluded that most protect against infection and severe or critical illness caused by the virus. In addition, the Johnson and Johnson vaccine and the Cuban Soberana 2 vaccine “probably” reduced all-cause mortality.
The independent, international expert reviewers also found that there was little or no difference between the number of people experiencing serious side effects after vaccination compared to those who were unvaccinated.
The researchers, led by Isabelle Boutron, Professor of Epidemiology at Université Paris Cité and Director of Cochrane France, analysed published data from 41 randomised controlled trials of 12 different COVID vaccines, involving 433 838 people in various countries around the world. They assessed the certainty of the evidence and the risk of bias in the different studies.
The trials compared COVID vaccines with placebo, no vaccine, or each other, and were published before 5 November 2021. Most trials were no longer than two months in length.
The review found that the following vaccines reduced or probably reduced the risk of COVID infection compared to placebo: Pfizer/BioNTech, Moderna, CureVac COVID-19, Oxford-AstraZeneca, J&J, Sputnik V (Gam-COVID-Vac), Sinopharm (WIBP CorV and BBIBP-CorV), Bharat (Covaxin), Novavax and Soberana 2 (Finlay-FR-2). The following reduced or probably reduced the risk of severe or critical disease: Pfizer/BioNTech, Moderna, Janssen, Sputnik V, Bharat and Novavax. In addition, the J&J and Soberana 2 vaccines probably decreased the all-cause mortality risk. There were very few deaths recorded in all the trials and so evidence on mortality for the other vaccines is uncertain.
For most of the vaccines, vaccinated individuals reported more localised or temporary side effects compared no-treatment or placebo groups. These included tiredness, headache, muscle pains, chills, fever and nausea. With respect to the very rare side effects associated with some vaccines such as thrombosis, the team found that the reporting of these events was inconsistent, and the number of events reported in the trials was very low.
Given the evidence of efficacy of these vaccines, the researchers question whether further placebo-controlled trials are ethical. They suggest that further research compares new vaccines with those already in use.
A comparison of vaccinations has demonstrated that mRNA vaccines perform better against variants of concern (VOCs) than viral vector vaccines. Although they all effectively prevent severe disease by VOCs, the research published in PLOS Medicine suggests that people receiving a viral vector vaccine are more vulnerable to infection by new variants.
The Pfizer-BioNTech and Moderna are mRNA vaccines, which deliver genetic code to the bodies’ cells, whereas Oxford/AstraZeneca and J&J are viral vector vaccines which uses a modified virus to deliver instructions. J&J is delivered as a single dose while the rest are administered two weeks apart.
Marit J. van Gils at the University of Amsterdam, Netherlands, and colleagues, took blood samples from 165 healthcare workers, three and four weeks after first and second vaccination respectively, and for J&J at four to five and eight weeks after vaccination. Samples were collected before, and four weeks after a Pfizer-BioNTech booster.
Four weeks after the initial two doses, antibody responses to the original SARS-CoV-2 viral strain were highest in recipients of Moderna, followed closely by Pfizer-BioNTech, and were substantially lower in those who received viral vector vaccines. Tested against the VOCs Alpha, Beta, Gamma, Delta and Omicron, neutralising antibodies were higher in the mRNA recipients than the viral vector recipients. Neutralisation ability against VOCs was reduced in all vaccine groups, with the greatest reduction against Omicron. The Pfizer-BioNTech booster increased antibody responses in all groups with substantial improvement against VOCs, including Omicron.
The researchers caution that their AstraZeneca group was significantly older, because of safety concerns for the vaccine in younger age groups. As immune responses tend to weaken with age, this could affect the results. This group was also smaller because the Dutch government halted use for a period.
The first randomised trial of COVID boosters, published in The Lancet, has shown that six are safe and provoke strong immune responses. Participants have previously received a two-dose course of ChAdOx1-nCov19 (Oxford–AstraZeneca [ChAd]) or BNT162b2 (Pfizer-BioNTech [BNT]). The announcement comes just as the Omicron variant is beginning to spread around the world.
ChAd has now been deployed in more than 180 countries and BNT in more than 145 countries. Several studies show that two doses of ChAd and BNT confer 79% and 90% protection, respectively, against hospitalisation and death after six months. However, protection against COVID infection wanes in time, which has led to the consideration of boosters. However, there are currently little data on the comparative safety of COVID vaccines, and the immune responses they stimulate, when given as a third dose.
The COV-BOOST study looked at safety, immune response (immunogenicity) and side-effects (reactogenicity) of seven vaccines when used as a third booster jab. The vaccines studied were ChAd, BNT, NVX-CoV2373 (Novavax [NVX]), Ad26.COV2.S (Janssen [Ad26]), Moderna [mRNA1273], VLA2001 (Valneva [VLA]), and CVnCov (Curevac [CVn]).
“The side effect data show all seven vaccines are safe to use as third doses, with acceptable levels of inflammatory side effects like injection site pain, muscle soreness, fatigue. Whilst all boosted spike protein immunogenicity after two doses of AstraZeneca, only AstraZeneca, Pfizer-BioNTech, Moderna, Novavax, Janssen and Curevac did so after two doses of Pfizer-BioNTech”, commented Professor Saul Faust, trial lead.
“It’s really encouraging that a wide range of vaccines, using different technologies, show benefits as a third dose to either AstraZeneca or Pfizer-BioNTech. That gives confidence and flexibility in developing booster programmes here in the UK and globally, with other factors like supply chain and logistics also in play”, added Prof Faust.
“It’s important to note that these results relate only to these vaccines as boosters to the two primary vaccinations, and to the immune response they drive at 28 days. Further work will generate data at three months and one year after people have received their boosters, which will provide insights into their impact on long-term protection and immunological memory. We are also studying two of the vaccines in people who had a later third dose after 7-8 months although results will not be available until the new year.”
A randomised, phase 2 trial of seven booster vaccines was conducted, with the third doses given 10-12 weeks after initial two-dose courses of ChAd or BNT. The trial involved 2878 healthy participants between June 1st and June 30th 2021. Participants had received their first doses of ChAd or BNT in December 2020, January or February 2021, and second doses at least 70 days before enrolment for ChAd and at least 84 days for BNT. About half of participants received two doses of ChAd and half two doses of BNT. The control vaccine used was a meningococcal conjugate vaccine (MenACWY).
Participants were aged 30 or older, roughly half of whom were 70 or older. The average age of participants who received ChAd was 53 years in the younger age group and 76 years in the older age group. Average ages for BNT were 51 and 78 years, respectively.
Thirteen experimental and control arms of the trial (seven vaccines plus three at half dose and three control arms) were split into three participant groups. Group A received NVX, half dose NVX, ChAd, or a control. Group B received BNT, VLA, half dose VLA, Ad26 or a control. Group C received Moderna, CVn (development of which was halted in October 2021), half dose BNT, or a control.
Primary outcomes were adverse effects seven days after receiving a booster, and levels of antibodies targeting the SARS-CoV-2 Spike protein after 28 days, compared to controls. Secondary outcomes included the response of T cells to wild type, Alpha, Beta, and Delta variants.
Increases in anti-spike protein antibody levels after 28 days varied across the vaccines. After two doses of ChAd these ranged from 1.8 times higher to 32.3 times higher according to the booster vaccine used. Following two doses of BNT, the range was 1.3 times higher to 11.5 times higher. Significant T-cell responses were reported in several combinations.
At 28 days, all booster results were similar for participants aged 30-69 years and those aged 70 years or older. Boost ratios should be interpreted with caution, the authors caution, since they relate to immunogenicity rather than protection against disease, and the relationship between antibody levels at day 28 and long-term protection and immunological memory is unknown.
Reactions to all seven vaccines were similar, with fatigue, headache, and injection site pain most often reported. These were more commonly reported by those aged 30-69. 912 of the 2878 participants experienced a total of 1036 adverse events, 24 of which were severe.
A cloud of platelet factor 4 proteins interacting with the electrostatic surface of the Oxford vaccine, as seen through the computational microscope. Credit: Chun Kit Chan, Arizona State University
An international team of scientists believe they may have found a molecular mechanism behind the extremely rare blood clots linked to adenovirus vaccines.
Scientists led by a team from Arizona State University, Cardiff University and others worked with AstraZeneca to investigate vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome (TTS), a life-threatening condition seen in a very small number of people after receiving the Oxford-AstraZeneca or Johnson & Johnson vaccines.
“The mechanism which results in this condition, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), was unknown,” said Abhishek Singharoy, an Arizona State University scientist and corresponding author of the study who teamed up to lead an international effort to tease out the details.
Together, the team worked to solve the structural biology of the vaccine, and see the molecular details that may be at play, utilising state-of-the cryo-EM technology to analyse the AstraZeneca vaccine in minute detail. They sought to understand whether the ultra-rare side effect could be linked to the viral vector which is used in many vaccines, including those from Oxford/AstraZeneca and Johnson & Johnson.
Their findings suggest it is the viral vector – in this case, an adenovirus used to shuttle the coronavirus’ genetic material into cells – and the way it binds to platelet factor 4 (PF4) once injected that could be the potential mechanism.
In very rare cases, the scientists suggest, the viral vector may enter the bloodstream and bind to PF4, where the immune system then views this complex as foreign. They believe this misplaced immunity could result in the release of antibodies against PF4, which bind to and activate platelets, leading to clustering and blood clotting.
“It’s really critical to fully investigate the vector-host interactions of the vaccine at a mechanistic level,” said Singharoy. “This will assist in understanding both how the vaccine generates immunity, and how it may lead to any rare adverse events, such as VITT.”
Adenovirus expert Professor Alan Parker said: “VITT only happens in extremely rare cases because a chain of complex events needs to take place to trigger this ultra-rare side effect. Our data confirms PF4 can bind to adenoviruses, an important step in unravelling the mechanism underlying VITT. Establishing a mechanism could help to prevent and treat this disorder.”
“We hope our findings can be used to better understand the rare side effects of these new vaccines – and potentially to design new and improved vaccines to turn the tide on this global pandemic.”
The AstraZeneca and Johnson & Johnson vaccines both use an adenovirus to carry SARS-CoV-2 Spike proteins to trigger an immune response.
Since VITT was seen in both vaccines, scientists wondered whether the viral vector was involved. Additionally, neither the Moderna nor Pfizer vaccines, both mRNA vaccines, showed this effect.
Using cryo-EM technology to flash-freeze preparations of ChAdOx1, the adenovirus used in the AstraZeneca vaccine, they produce microscopic images of the vaccine components.
They were then able to view the viral capsid structure and other critical proteins that allow entry of the virus into the cell.
In particular, the team outlined the details for the structure and receptor of ChAdOx1, which is adapted from chimpanzee adenovirus Y25 – and how it interacts with PF4. They believe it is this specific interaction – and how it is then presented to the immune system – that could cuase the immune system to see it as foreign and release antibodies against this self-protein.
The research team also used computational models to show that one of the ways the two molecules tightly bind is via electrostatic interactions. The group showed that ChAdOx1 is mostly electronegative, attracting other positively charged molecules to its surface.
First author Dr Alexander Baker said: “We found that ChAdOx1 has a strong negative charge. This means the viral vector can act like a magnet and attract proteins with the opposite, positive charge, like PF4.” Baker is a member of ASU’s Biodesign Center for Applied Structural Discovery and an Honorary Research Fellow at Cardiff University School of Medicine.
“We then found that PF4 is just the right size and shape that when it gets close to ChAdOx1 it could bind in between the negatively charged parts of ChAdOx1’s surface, called hexons.”
The research team are hopeful that armed with a better understanding of what may be causing rare VITT they can provide further insights into how vaccines and other therapies, which rely on the same technology, might be altered in the development of the next generation vaccines and therapies.
“With a better understanding of the mechanism by which PF4 and adenoviruses interact there is an opportunity to engineer the shell of the vaccine, the capsid, to prevent this interaction with PF4. Modifying ChAdOx1 to reduce the negative charge may reduce the chance of causing thrombosis with thrombocytopenia syndrome,” said Baker.
The team likened it to the ‘two birds, one stone’ effect. The key contacts of individual amino acids that are essential to the capsid protein’s proteins interaction with PF4 can removed or substituted.
“The modification of the ChAdOx1 hexons to reduce their electronegativity may solve two problems simultaneously: reduce the propensity to cause VITT to even lower levels, and reduce the levels of pre-existing immunity, thus helping to maximize the opportunity to induce robust immune responses, said Singharoy.”
A new study has found no association between COVID vaccinations and risk of first-trimester miscarriages, providing further evidence of the safety of COVID vaccination during pregnancy. The findings were published in the New England Journal of Medicine.
Study co-author Dr Deshayne Fell said, “The study analysed several national health registries in Norway to compare the proportion of vaccinated women who experienced a miscarriage during the first trimester and women who were still pregnant at the end of the first trimester.” Dr Fell, is Associate Professor in the School of Epidemiology and Public Health in the University of Ottawa’s Faculty of Medicine and a Scientist at the Children’s Hospital of Eastern Ontario (CHEO) Research Institute.
“Our study found no evidence of an increased risk for early pregnancy loss after COVID vaccination and adds to the findings from other reports supporting COVID vaccination during pregnancy,” the study authors wrote.
“The findings are reassuring for women who were vaccinated early in pregnancy and support the growing evidence that COVID vaccination during pregnancy is safe.”
Dr Fell and colleagues found no relationship between the type of vaccine received and miscarriage. In Norway, the vaccines used included Pfizer, Moderna and AstraZeneca.
“It is important that pregnant women are vaccinated since they have a higher risk of hospitalisations and COVID-complications, and their infants are at higher risk of being born too early. Also, vaccination during pregnancy is likely to provide protection to the newborn infant against COVID infection in the first months after birth,” the study authors stressed.
The Oxford-AstraZeneca vaccine’s success against SARS-CoV-2 has prompted scientists to develop a vaccine for cancer, using Oxford’s viral vector vaccine technology.
When tested in mouse tumour models, the two-dose therapeutic cancer vaccine increased the numbers of anti-tumour T cells infiltrating the tumours and improved the efficacy of cancer immunotherapy. Compared to immunotherapy alone, combination with the vaccine resulted in a greater reduction in tumour size and improved survival.
The study, which was done by Professor Benoit Van den Eynde’s group at the Ludwig Institute for Cancer Research, University of Oxford in collaboration with co-authors Professor Adrian Hill and Dr Irina Redchenko at the University’s Jenner Institute, has been published in the Journal for ImmunoTherapy of Cancer.
Cancer immunotherapy has improved outcomes for some cancer patients. Anti-PD-1 immunotherapy works by unleashing anti-tumour T cells to allow them to kill cancer cells. However, in the majority of cancer patients, anti-PD-1 therapy is still ineffective .
One reason for the poor efficacy of anti-PD-1 cancer therapy is that some patients have low levels of anti-tumour T cells. Oxford’s vaccine technology generates strong CD8+ T cell responses, which are necessary for strong anti-tumour effects.
The team developed a two-dose therapeutic cancer vaccine with different prime and boost viral vectors, one of which is the same as the vector in the Oxford-AstraZeneca COVID vaccine. In order to create a vaccine treatment that specifically targets cancer cells, the vaccine was designed to target two MAGE-type proteins found on the surface of many types of cancer cells.
Preclinical experiments in mouse tumour models demonstrated that the cancer vaccine increased the levels of tumour-infiltrating CD8+ T cells and enhanced the response to anti-PD-1 immunotherapy. The combined vaccine and anti-PD-1 treatment resulted in a greater reduction in tumour size and improved the survival of the mice compared to anti-PD-1 therapy alone.
Benoit Van den Eynde, Professor of Tumour Immunology at the University of Oxford, said: “We knew from our previous research that MAGE-type proteins act like red flags on the surface of cancer cells to attract immune cells that destroy tumours.
“MAGE proteins have an advantage over other cancer antigens as vaccine targets since they are present on a wide range of tumour types. This broadens the potential benefit of this approach to people with many different types of cancer.
“Importantly for target specificity, MAGE-type antigens are not present on the surface of normal tissues, which reduces the risk of side-effects caused by the immune system attacking healthy cells.”
Human trials in 80 patients with non-small cell lung cancer will be launched later this year.
Adrian Hill, Lakshmi Mittal and Family Professorship of Vaccinology and Director of the Jenner Institute, University of Oxford, said: “This new vaccine platform has the potential to revolutionise cancer treatment. The forthcoming trial in non-small cell lung cancer follows a Phase 2a trial of a similar cancer vaccine in prostate cancer undertaken by the University of Oxford that is showing promising results.
“Our cancer vaccines elicit strong CD8+ T cell responses that infiltrate tumours and show great potential in enhancing the efficacy of immune checkpoint blockade therapy and improving outcomes for patients with cancer.”
Interim results from a phase 1B/2A clinical trial conducted by the Wits Vaccines and Infectious Diseases Analytical (VIDA) research unit showed that the AstraZeneca vaccine conferred COVID protection in people living with HIV.
The findings, published in Lancet HIV, show that the AstraZeneca COIVD vaccine is likely to work as well in people living with HIV compared with people who are HIV negative.
These interim findings are vital for informing the clinical management of people with HIV during the COVID pandemic.
In general, clinical trials which evaluate the safety and immunogenicity of COVID vaccines in people living with HIV are limited, and in Africa they are virtually non-existent. This is despite the overwhelming prevalence of HIV infection in Africa, especially South Africa .
“We searched PubMed for peer-reviewed articles published between 1 January 2019 and 29 June 2021, using the terms ‘safety’ and ‘Covid-19’ and ‘vaccine’, but we did not find any reports that evaluated safety and immunogenicity of COVID vaccines in this population,” said Shabir Madhi, Professor of Vaccinology and Director of Wits VIDA, which led the first South African trial for a COVID vaccine in June 2020.
Compared to the general population, people living with HIV have an increased risk of infectious diseases and have a greater mortality risk when hospitalised with severe COVID.
In addition, compared with HIV-negative individuals, people with HIV are at greater risk for infectious diseases, such as influenza, including during antiretroviral therapy (ART).
Risk factors for severe COVID in people with HIV include more advanced stage of HIV/AIDS, the HIV-1 infection not being virally suppressed, and CD4 counts below 500 cells per microlitre.
The study was an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial. In 2020, the trial enrolled 104 people living with HIV were enrolled in the trial, HIV-negative people. Eligibility criteria for people with HIV included being on ART for at least three months, with a plasma HIV viral load of less than 1000 copies per microlitre.
The HIV study was a unique addition to the AstraZeneca COVID vaccine clinical trial, and aimed to assess safety and immunogenicity of this vaccine in people with HIV and HIV-negative people in South Africa. The primary endpoint in all participants regardless of HIV status was the safety, tolerability, and reactogenicity profile of the AstraZeneca COVID vaccine.
Reactogenicity refers to a subset of reactions that occur soon after vaccination, and are a physical manifestation of the inflammatory response to vaccination. Such symptoms include pain, redness, swelling or induration for injected vaccines, and systemic symptoms, such as fever, myalgia, headache, or rash. In clinical trials, information on expected signs and symptoms after vaccination is actively sought.
The interim findings show that the AstraZeneca COVID vaccine was well tolerated and showed favourable safety and immunogenicity in people with HIV, including heightened immunogenicity in SARS-CoV-2 baseline-seropositive participants.
A COVID prophylactic cocktail of long-acting antibodies cut the risk of developing symptomatic disease in a high-risk unvaccinated patient population, AstraZeneca announced on Friday.
Initial phase III trial data showed that AZD7442 (tixagevimab and cilgavimab) as pre-exposure prophylaxis significantly reduced the risk of developing COVID symptoms by 77% versus placebo, meeting the trial’s primary endpoint. AstraZeneca further noted there were no cases of severe COVID or COVID-related deaths in the intervention group, while there were three cases of severe COVID and two deaths in the placebo group.
No safety concerns were noted by the manufacturer, as the treatment was well-tolerated and adverse events were balanced between groups.
A key feature of the trial was that 75% of participants had comorbidities, including being “at risk of an inadequate response to active [immunisation],” such as older adults and those with immunosuppressive disease or on immunosuppressive medication.
“With these exciting results, AZD7442 could be an important tool in our arsenal to help people who may need more than a vaccine to return to their normal lives,” the trial’s principal investigator, Myron Levin, MD, of the University of Colorado School of Medicine, said in a statement.
AZD7442 was derived from the B cells of convalescent patients. PROVENT was a phase III randomised trial conducted in the US and Europe. Participants were 5197 adults “who would benefit from prevention” with the long-acting antibody, were unvaccinated at the time of enrollment, and tested negative for SARS-CoV-2. Participants were randomised 2:1 to receive a single 300 mg dose of AZD7442 or placebo. AstraZeneca noted that 43% of participants were ages 60 and older. The company noted that the drug is active in lab studies against emerging strains, including the Delta variant.
Patients were followed for 183 days, though subjects are slated to be followed for 15 months, AstraZeneca said. Data will be submitted for peer-reviewed publication while the company seeks approval for AZD7442.
A UK study has furthered the understanding of the novel blood-clotting condition associated with the Oxford/AstraZeneca vaccine.
Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is characterised by a blockage of veins and a marked platelet reduction. The rare condition was first identified in the UK by Professor Marie Scully (University College of London Institute of Cardiovascular Science), also a Consultant Haematologist at UCLH, and Dr Will Lester from University Hospitals Birmingham NHS Foundation Trust.
In a paper published in the New England Journal of Medicine (NEJM), the first 220 cases of definite and probable VITT in the UK are detailed.
The cases were presented by 182 consultant haematologists, and builds on understanding about the condition outlined in an April 2021 NEJMpaper led by Professor Scully.
Meanwhile, a study led by Dr Richard Perry (UCL Queen Square Institute of Neurology and UCLH) published in the Lancetearlier this month provided the most detailed observations so far of cases of cerebral venous thrombosis (CVT). one of the commonest and severest manifestations of VITT.
The overall mortality rate of those presenting to hospitals with definite or probable VITT was 23%, the paper reported. The condition almost entirely manifested between five and 30 days after their first vaccination, with no sex differences seen, and no predisposing prior medical conditions.
The chances of death increased significantly the lower the platelet count and the greater the activation of the blood clotting system, increasing to 73% in patients with a very low platelet count and intracranial haemorrhage following blood clots in the brain.
Overall, 41% of patients had no previous medical diagnoses and 85% were less than 60 years old. Overall incidence in individuals under 50 was estimated to be 1 in 50 000 – in line with reports from other countries.
Though optimal treatment was still uncertain, it was being continually refined in real time, the researchers wrote. For instance, the introduction of the use of plasma exchange in the most severe cases has led to survival rates that were significantly better than would be predicted based on baseline characteristics.
The research adds to evidence for use of non-heparin-based blood thinners to tackle blood clotting in cases of VITT, and that use of intravenous immunoglobin was associated with better outcomes.
Professor Scully said: “As a new condition we are still learning about how best to diagnose and manage VITT, but as time goes on, we have been able to refine our treatment approaches and improve rates of survival and chance of recovery. This continuous learning in real time has been made possible thanks to collaboration between colleagues across the UK.”
Lead author Dr Sue Pavord, at Oxford University Hospitals NHS Foundation Trust, said: “We have worked relentlessly to understand and manage this new condition, so that the hugely successful vaccine roll out can continue, which is the most viable solution to the global pandemic.”
A multi-institutional team of researchers has found that administering the AstraZeneca COVID vaccine intranasally to infected hamsters and monkeys reduced viral loads in nasal swabs, suggesting reduced shedding.
The group describes the testing they conducted with COVID-infected animals and the possible implications of their work, in their paper published in the journal Science Translational Medicine.
Another COVID surge is occurring in a number of countries where vaccinations are readily available, likely due to the arrival of new variants and wide resistance to the vaccinations. Breakthrough infections have been reported in vaccinated individuals. These has resulted in renewed calls for mask-wearing, even in vaccinated individuals. This is because it is not yet clear if vaccinated people can infect other people, even if they have no symptoms. In this new effort, the researchers suggest that adding intranasal inoculation to vaccination efforts might help.
Currently, the vast majority of vaccines developed and in use are intramuscular, given via shots in the arm. Recently, a team at the University of Alabama noted that an intranasal administration of COVID vaccines would seem to make more sense, since COVID is a disease of the nose, throat and lungs. In this new study, the researchers have given an already existing COVID vaccine intranasally to test animals with COVID to see what would happen.
They found that intranasal administration of the AstraZeneca vaccine to infected hamsters and monkeys led to lowered viral loads on nasal swabs, indicating that intranasal administration reduces viral shedding and thereby transmissibility of the virus.
Unfortunately, prior research has also shown that vaccines given intranasally confer immunity for a shorter period of time than intramuscular vaccination. Thus, as the team in Alabama noted, the best approach might turn out to be a combination of a shot in the arm along with a puff of mist up the nose to confer both short-term and long-term protection.
