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Coronavirus Research Tracking - 5 November - Vaccine edition

Coronavirus Research Tracking - 5 November - Vaccine edition

This article was published on
November 5, 2021

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This week, comparing the immune effective of vaccinations and natural infections, the benefits of a prior infection plus vaccination, effectiveness of mixing-and-matching vaccines and third doses, a skin patch vaccine delivery system, modifying vaccines for variants, comparing the neurological risks from Covid-19 and vaccinations, and the effectiveness of vaccines for immunocompromised people. It is easy to get swamped by all the research on coronavirus. New Zealand’s Science Media Centre is keeping track of much of it so you don’t have to. The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre New Zealand.

This week, comparing the immune effective of vaccinations and natural infections, the benefits of a prior infection plus vaccination, effectiveness of mixing-and-matching vaccines and third doses, a skin patch vaccine delivery system, modifying vaccines for variants, comparing the neurological risks from Covid-19 and vaccinations, and the effectiveness of vaccines for immunocompromised people. It is easy to get swamped by all the research on coronavirus. New Zealand’s Science Media Centre is keeping track of much of it so you don’t have to. The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre New Zealand.

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Vaccination provides greater protection than a prior infection

The odds of becoming reinfected after an earlier infection were 5.5-fold higher than becoming infected after mRNA vaccinations, a US study reports. This study looked at only people who were hospitalised, and had a prior infection or vaccination three to six months earlier. The effectiveness of infection followed by vaccination was not studied.

It was not possible to determine if infection risk changed based on time since prior infection or vaccination. Vaccinated people 65 or older were less likely than younger participants to become infected. The Moderna vaccine provided a higher level of effectiveness than the Pfizer/BioNTech vaccine. The paper was published in the Morbidity and Mortality Weekly Report.

Prior infection plus vaccination can provide the strongest protection

A Qatari study found that prior infection halved the risk of an infection after vaccination. The probability of a breakthrough infection was significantly lower for those infected at least six months before vaccination, compared to those who were vaccinated less than six months after an infection.

For those without a prior infection, the incidence of breakthrough infections increased as time since the second vaccine dose increased, suggesting waning effectiveness.

The Moderna vaccine appeared to be more effective in reducing infection risk than the Pfizer/BioNTech vaccine, although direct comparisons were not possible. The authors suggest that the one week longer gap between doses and the higher mRNA concentration in the Moderna vaccine may contribute to greater effectiveness, but this isn’t proven.  

Over 1.5 million mRNA vaccinated people were included in the study. The paper was published in JAMA.


A US study found that six months after vaccination those who had a prior infection had higher antibody levels. Similar to the Qatari study, a longer interval between infection and the first vaccine dose led to a stronger immune response six months after vaccination. The study involved healthcare workers, who were mostly female, white, and middle-aged, so it is not generalisable. The paper was published in JAMA.

Third dose of Pfizer/BioNTech very effective at reducing severe symptoms

A large Israeli study reports that a third Pfizer/BioNTech dose is very effective at reducing risks of hospitalisations, more severe Covid-19, and death. The matched study compared over 700,000 people who received a third dose at least five months after the second with the same number who had only had two doses.

Vaccine effectiveness after a third dose was 93% for hospitalisation, 92% for severe disease, and 81% for Covid-related death. These were assessed at least seven days after the third vaccine dose. There were too few hospitalised Covid cases for those under 40 to compare effectiveness in this age group. The paper was published in The Lancet.

Mix-and-Match improves AstraZeneca effectiveness

A Canadian study reports that combining an AstraZeneca/Oxford vaccine dose with an mRNA dose leads to greater effectiveness against infection than two AstraZeneca doses. Effectiveness with a mixed dose was over 90%, compared with 70% for two AstraZeneca doses. Two mRNA doses also provided over 90% effectiveness.

Both vaccines, whether mixed or not, provided around 95% effectiveness against hospitalisation at least four months after the second dose. Effectiveness against infection declined somewhat over time, dropping to about 80% for mRNA vaccines after five to seven months.

The study also found that a timing of 7-8 weeks between the two doses provided the greatest effectiveness for both vaccines. The study used a test-negative design to reduce some observational biases. The paper has not yet been peer reviewed.

Rising summer infections in the UK driven by Delta variant and unvaccinated young people

Overall vaccine effectiveness against infection from any variant in the UK has been estimated to have been between 49% and 62% in June and July 2021. The range reflects whether an infection was inferred from symptoms or PCR test results. Vaccine effectiveness against serious disease was over 90%.

This on-going study (called REACT-1) also reports that the rise in infections during June and July is attributable to the greater transmissibility of the Delta variant and the increasing number of younger (13 to 24 year olds) unvaccinated people becoming infected. The authors note that greater social mixing is likely to continue to drive infection rates even when vaccination levels are high. The results rely on self-reporting of infection and vaccination status. The paper was published in Science.

Robust persistent T cell response from Pfizer/BioNTech vaccine

The Pfizer/BioNTech vaccine generates antiviral T cell (CD4+ & CD8+) responses for at least six months. Results are based on 71 vaccinated healthcare workers. The paper was published in Science Immunology.

Modified Inovio vaccine provides stronger neutralisation activity against variants

A second dose of the DNA vaccine INO-4800, or a modified version, one year after the first dose boosted immune responses in macaques. The modified vaccine (INO-4802) has a more general spike sequence to provide greater protection against variants. Both the original and the modified vaccines boosted neutralising antibodies substantially, compared with levels before the second dose.

The antibodies were able to neutralise wild-type and pseudovirus variants of concern. Neutralising activity against Beta and Gamma variants was higher for the INO-4802 vaccine. Only four or five animals were given a second dose. The vaccines are produced by Inovio Pharmaceuticals and are still undergoing clinical trials. The paper has not yet been peer reviewed.

Skin patch vaccine delivery system looks promising

A skin patch vaccine delivery system generated a stronger immune response in mice than delivering the same vaccine by syringe. The skin patch provided complete protection against Covid-19 disease. The vaccine was a subunit type, involving part of the spike protein. Only small numbers of mice were used in the tests. The paper was published in Science Advances.

Neurological risks from AstraZeneca and Pfizer vaccines lower than from infection

The risk of neurological complications is greater following SARS-CoV-2 infection than after vaccination. This is based on an analysis of 32 million health records in the UK.

There were increased risks of hospitalisations for Guillain–Barré syndrome, Bell’s palsy and myasthenic disorders in those who received the AstraZeneca/Oxford vaccine. However, the risks were still very low. For example, an excess of 38 cases of Guillain–Barré for 10 million vaccinations. For those receiving the Pfizer/BioNTech vaccine there was an increased risk for hemorrhagic stroke (60 excess cases per 10 million).

The risks of these, and other neurological conditions, were much higher from infections. For example, the risk of Guillain–Barré syndrome for those with a SARS-CoV-2 infection was 145 excess cases per 10 million. Risks were assessed in the 28 days after the first vaccine dose or an infection. The paper was published in Nature Medicine.

Vaccines effective for immunocompromised people

Immunocompromised people benefit from being vaccinated with the mRNA vaccines. Effectiveness levels against severe Covid-19 were about 70% (non-immunocompromised people typically have about 90% effectiveness). For people who had received organ or stem cell transplants effectiveness was lower (around 60%) than for other immunocompromised groups.

The authors agree with CDC recommendations that immunocompromised people should receive three mRNA doses, followed by a fourth dose six months after the third dose. The paper was published in Morbidity and Mortality Weekly Report.

Subscribe to SMC-NZ's Coronavirus Research Tracker.

Vaccination provides greater protection than a prior infection

The odds of becoming reinfected after an earlier infection were 5.5-fold higher than becoming infected after mRNA vaccinations, a US study reports. This study looked at only people who were hospitalised, and had a prior infection or vaccination three to six months earlier. The effectiveness of infection followed by vaccination was not studied.

It was not possible to determine if infection risk changed based on time since prior infection or vaccination. Vaccinated people 65 or older were less likely than younger participants to become infected. The Moderna vaccine provided a higher level of effectiveness than the Pfizer/BioNTech vaccine. The paper was published in the Morbidity and Mortality Weekly Report.

Prior infection plus vaccination can provide the strongest protection

A Qatari study found that prior infection halved the risk of an infection after vaccination. The probability of a breakthrough infection was significantly lower for those infected at least six months before vaccination, compared to those who were vaccinated less than six months after an infection.

For those without a prior infection, the incidence of breakthrough infections increased as time since the second vaccine dose increased, suggesting waning effectiveness.

The Moderna vaccine appeared to be more effective in reducing infection risk than the Pfizer/BioNTech vaccine, although direct comparisons were not possible. The authors suggest that the one week longer gap between doses and the higher mRNA concentration in the Moderna vaccine may contribute to greater effectiveness, but this isn’t proven.  

Over 1.5 million mRNA vaccinated people were included in the study. The paper was published in JAMA.


A US study found that six months after vaccination those who had a prior infection had higher antibody levels. Similar to the Qatari study, a longer interval between infection and the first vaccine dose led to a stronger immune response six months after vaccination. The study involved healthcare workers, who were mostly female, white, and middle-aged, so it is not generalisable. The paper was published in JAMA.

Third dose of Pfizer/BioNTech very effective at reducing severe symptoms

A large Israeli study reports that a third Pfizer/BioNTech dose is very effective at reducing risks of hospitalisations, more severe Covid-19, and death. The matched study compared over 700,000 people who received a third dose at least five months after the second with the same number who had only had two doses.

Vaccine effectiveness after a third dose was 93% for hospitalisation, 92% for severe disease, and 81% for Covid-related death. These were assessed at least seven days after the third vaccine dose. There were too few hospitalised Covid cases for those under 40 to compare effectiveness in this age group. The paper was published in The Lancet.

Mix-and-Match improves AstraZeneca effectiveness

A Canadian study reports that combining an AstraZeneca/Oxford vaccine dose with an mRNA dose leads to greater effectiveness against infection than two AstraZeneca doses. Effectiveness with a mixed dose was over 90%, compared with 70% for two AstraZeneca doses. Two mRNA doses also provided over 90% effectiveness.

Both vaccines, whether mixed or not, provided around 95% effectiveness against hospitalisation at least four months after the second dose. Effectiveness against infection declined somewhat over time, dropping to about 80% for mRNA vaccines after five to seven months.

The study also found that a timing of 7-8 weeks between the two doses provided the greatest effectiveness for both vaccines. The study used a test-negative design to reduce some observational biases. The paper has not yet been peer reviewed.

Rising summer infections in the UK driven by Delta variant and unvaccinated young people

Overall vaccine effectiveness against infection from any variant in the UK has been estimated to have been between 49% and 62% in June and July 2021. The range reflects whether an infection was inferred from symptoms or PCR test results. Vaccine effectiveness against serious disease was over 90%.

This on-going study (called REACT-1) also reports that the rise in infections during June and July is attributable to the greater transmissibility of the Delta variant and the increasing number of younger (13 to 24 year olds) unvaccinated people becoming infected. The authors note that greater social mixing is likely to continue to drive infection rates even when vaccination levels are high. The results rely on self-reporting of infection and vaccination status. The paper was published in Science.

Robust persistent T cell response from Pfizer/BioNTech vaccine

The Pfizer/BioNTech vaccine generates antiviral T cell (CD4+ & CD8+) responses for at least six months. Results are based on 71 vaccinated healthcare workers. The paper was published in Science Immunology.

Modified Inovio vaccine provides stronger neutralisation activity against variants

A second dose of the DNA vaccine INO-4800, or a modified version, one year after the first dose boosted immune responses in macaques. The modified vaccine (INO-4802) has a more general spike sequence to provide greater protection against variants. Both the original and the modified vaccines boosted neutralising antibodies substantially, compared with levels before the second dose.

The antibodies were able to neutralise wild-type and pseudovirus variants of concern. Neutralising activity against Beta and Gamma variants was higher for the INO-4802 vaccine. Only four or five animals were given a second dose. The vaccines are produced by Inovio Pharmaceuticals and are still undergoing clinical trials. The paper has not yet been peer reviewed.

Skin patch vaccine delivery system looks promising

A skin patch vaccine delivery system generated a stronger immune response in mice than delivering the same vaccine by syringe. The skin patch provided complete protection against Covid-19 disease. The vaccine was a subunit type, involving part of the spike protein. Only small numbers of mice were used in the tests. The paper was published in Science Advances.

Neurological risks from AstraZeneca and Pfizer vaccines lower than from infection

The risk of neurological complications is greater following SARS-CoV-2 infection than after vaccination. This is based on an analysis of 32 million health records in the UK.

There were increased risks of hospitalisations for Guillain–Barré syndrome, Bell’s palsy and myasthenic disorders in those who received the AstraZeneca/Oxford vaccine. However, the risks were still very low. For example, an excess of 38 cases of Guillain–Barré for 10 million vaccinations. For those receiving the Pfizer/BioNTech vaccine there was an increased risk for hemorrhagic stroke (60 excess cases per 10 million).

The risks of these, and other neurological conditions, were much higher from infections. For example, the risk of Guillain–Barré syndrome for those with a SARS-CoV-2 infection was 145 excess cases per 10 million. Risks were assessed in the 28 days after the first vaccine dose or an infection. The paper was published in Nature Medicine.

Vaccines effective for immunocompromised people

Immunocompromised people benefit from being vaccinated with the mRNA vaccines. Effectiveness levels against severe Covid-19 were about 70% (non-immunocompromised people typically have about 90% effectiveness). For people who had received organ or stem cell transplants effectiveness was lower (around 60%) than for other immunocompromised groups.

The authors agree with CDC recommendations that immunocompromised people should receive three mRNA doses, followed by a fourth dose six months after the third dose. The paper was published in Morbidity and Mortality Weekly Report.

Subscribe to SMC-NZ's Coronavirus Research Tracker.

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