Coronavirus Research Tracking - 17 September - vaccine edition

Important studies on booster shots and vaccine effectiveness, comparing vaccines, vaccination risks in boys

This week there are lots of vaccine-related studies. Emerging evidence on the effectiveness of a booster dose for the Pfizer/BioNTech vaccine, and effectiveness of several vaccines in general, as well as against the Delta variant. Plus, comparing immune responses to different vaccines, evidence for vaccines reducing transmissibility, and vaccine-related myocarditis risks for boys.

Non-vaccine-related papers are in a separate Tracker again today.

The tracker is shared with the COVID-19 Vaccine Media Hub.

The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.

Vaccine-related papers

Pfizer requests approval for a third dose

Pfizer’s submission to the FDA recommends a third vaccine dose for everyone over 16. It reviews existing evidence and concludes that vaccine effectiveness against infection declines about 6% every two months (as reported in a just published article in The New England Journal of Medicine).

Pfizer concludes that waning vaccine effective against infection rather than better immune avoidance by the Delta variant explain the recent decline in protection.

Pfizer claims that a third dose, given 6 months after the second, would increase effectiveness back to 95%. Research to date indicates a third dose would be safe.

This is based on another Israeli study. It found that 12 days after a third Pfizer/BioNTech dose infections were 11-fold lower than in a comparable group with no booster. The incidence of severe illness was 19.5 times lower. Participants were 60 years or older, and received their second vaccine dose at least five months earlier. The paper was also published in The New England Journal of Medicine.

There is as yet no indication of how long such a level of effectiveness would be maintained after a third dose. The FDA said it will release its assessment “as quickly as possible.”

Moderna may seek one too

Moderna has also just indicated that there may be waning immunity for their vaccine. Reference is made to a decline in effectiveness against infection about 8 months after vaccination, but a paper based on this data has not yet been made public.

Earlier this month a study of real-world effectiveness of the Moderna vaccine found relatively stable protection four to five months after vaccination. Effectiveness against infection was 87·4%, 95·8% against Covid-19 hospitalisation, and 97·9% against death due to Covid-19. Vaccine effectiveness was higher for symptomatic infections than for asymptomatic cases, similar to results for the Pfizer/BioNTech vaccine. The paper has not yet been peer reviewed.

Gradual decline in effectiveness against infection over 6 months for Pfizer/BioNTech vaccine

A large scale trial reports that over six months the Pfizer/BioNTech vaccine showed a gradual decline in effectiveness against infection. However, it still provided strong protection (over 80%) beyond four months. The two doses were given three weeks apart. The paper was published in The New England Journal of Medicine.

But initial rapid then gradual decline of effectiveness against severe Covid-19

The dynamics of vaccine effectiveness vary depending on the time frames being studied and what type of effectiveness is being examined. Vaccination strategies and population characteristics can also influence results.

A study from Scotland found that vaccine effectiveness against severe Covid-19 declined initially as Delta spread in May, but then stabilised. Three vaccines were being used (AstraZeneca/Oxford and the two mRNA vaccines). The authors interpret the results as a rapid early waning (over 2 months) of efficacy after the second vaccine dose, followed by a slower decline, rather than immune escape by the Delta variant. Efficacy against hospitalisation and death stabilised to around 80% after several months.

Effectiveness against severe Covid for all three vaccines was similar (just over 90%), although AstraZeneca/Oxford was less effective when a broader category including hospitalisation and death was considered.

The authors suggest that booster shots may best be targeted to those most at risk, rather than be available for all. They also note that the longer term effectiveness of the vaccines is unknown. The paper has not yet been peer reviewed.

Vaccines effective against Delta variant, particularly for those under 65

Three independent papers in the CDC’s Morbidity and Mortality Weekly Report describe vaccination effectiveness against hospitalisation. They all show that effectiveness remains high for the Delta variant, at least for those under 65.

One paper found that hospitalisation and death rates due to Covid-19 changed little after the spread of the Delta variant. Risk of infection increased in fully vaccinated people in June and July, compared with April and May (when the Alpha variant was dominant).

In June and July the infection risk after full vaccination was calculated to be 5 times lower than for those unvaccinated or partially vaccinated. The risks of hospitalisation and death were more than 10 times lower.

A second paper found that effectiveness against hospitalisation and emergency care remained high (over 80%) against the Delta variant infections. There was, though, lower vaccine effectiveness against hospitalisation for those over 75 (76%) than for younger people (89%).  This difference appears higher for Delta than earlier variants. 

Comparing different vaccines, effectiveness was significantly higher for the Moderna vaccine (95%), compared with Pfizer/BioNTech (80%) and Johnson & Johnson/Janssen (60%). Time since vaccination was not analysed.

The third paper reported higher vaccine effectiveness against hospitalisation in those under 65 (95%) than over 65s (80%). These figures are based on five Veterans Affairs medical centres and hospitalisations between February and August.

This study also found vaccine effectiveness against hospitalisation was similar before and after Delta became dominant.

Benefits of vaccination in England

Public Health England’s latest weekly vaccine surveillance report notes that 95% of adults aged 17 or older have antibodies from either infection or vaccination. It estimates that the vaccination programme in England has directly averted over 143,600 hospitalisations, prevented between 24.4 and 24.9 million infections and between 108,600 and 116,200 deaths.

Vaccination effects on transmissibility

A review of existing research concludes that vaccinations do reduce secondary infections. This is due to a combination of factors, including reducing viral replication and the proportion of symptomatic cases. The paper also recommends developing oral and nasal vaccines, which would probably decrease transmissibility more effectively. The paper was published in The Lancet Infectious Diseases.

Oral and nasal vaccines that target the mucosa are already in development, and showing encouraging results. For example, this study of an oral vaccine, which has not yet been peer reviewed.

An outbreak in vaccinated nursing home residents

A French study describes an outbreak in a nursing home where nearly all residents were vaccinated. Median age of residents was 88, and 72 of the 74 were vaccinated (with Pfizer/BioNTech). The outbreak was due to a resident becoming infected outside of the home. 

Sixteen (22%) of the vaccinated became infected, with seven developing severe Covid-19 and two requiring hospitalisation. One of the two unvaccinated became infected, and subsequently died. The infections were caused by the Alpha variant.

The authors note that while the vaccine reduces risks of hospitalisation and death, other health measures are also required in aged care facilities. The paper was published in JAMA Network Open.

Pfizer/BioNTech and Sinovac vaccines produce different antibody responses

A large Chilean study found that the Pfizer/BioNTech vaccine produced stronger and more prolonged antibody responses than Sinovac’s CoronaVac vaccine. The latter is based on an inactivated virus.

Three weeks after the second doses, 77% of those receiving CoronaVac had detectable IgG antibodies, compared with 95% for the Pfizer vaccine. Seropositivity in CoronaVac recipients then declined, while levels remained stable for the next four months for those vaccinated with the Pfizer vaccine.

Whether these differences result in different levels of protection is unknown. Neutralisation antibodies were not assessed. The paper was published in The Lancet Infectious Diseases.

Bharat Biotech and AstraZeneca/Oxford vaccines also produce different antibody responses

An Indian study found significant declines in antibody levels four months after vaccination for two vaccines. The vaccines were Covaxin (BBV-152, developed by Bharat Biotech International) and AstraZeneca/Oxford (called Covishield in India). Covishield produced significantly higher levels of IgG antibodies than Covaxin. The proportion of seropositivity cases was also considerably higher for Covishield. The implications for immunity are not yet known. The paper has not yet been peer reviewed.

MMR vaccine may prime immune system for SARS-CoV-2 response

Previous vaccinations with the measles-mumps-rubella (MMR) or tetanus-diphtheria-pertussis vaccines may help reduce Covid-19 symptom severity. These vaccines produce a similar T cell population as that generated after SARS-CoV-2 infection or vaccination with mRNA vaccines. 

The authors of this paper suggest that SARS-CoV-2 infection may help reactivate memory T cells, leading to more rapid control of symptoms. The research reports correlations only, and relied on self-reporting of whether participants had had the MMR or tetanus vaccines. The paper was published in Med.

A commentary on the paper was also published in the same issue of Med.  

People with obesity may have weaker antibody responses to vaccines

Vaccine responses in people with obesity have not yet been well studied. An Italian study reports that after vaccination peak antibody levels were lower in people with abdominal obesity, compared with those who were not obese. Three months after vaccination the decline in antibody levels was also greater for those who had obesity.

Antibody levels declined 2.44 fold in the abdominal obesity group and 1.82-fold in the control group. The trial involved the Pfizer/BioNTech vaccine, and participants did not have evidence of previous SARS-CoV-2 infections. The extent to which the differences in antibody levels affects infection and disease severity risks is unknown. The paper has not yet been peer reviewed

A position statement from The Obesity Society, published in July in Obesity, concluded on available evidence at the time that the efficacy of the Pfizer/BioNTech, Moderna and Johnson & Johnson/Janssen vaccines were safe and effective for people with obesity.

Myocarditis risks in vaccinated adolescents

Pfizer/BioNTech vaccination-associated myocarditis incidence is much higher in young (12-17 years old) males than females. In this study the likelihood of post-vaccination cardiac problems in 12 to 15 year old boys without health comorbidities was 162.2 per million adolescents, and 94.0/million for 16 to 17 year olds. The rates in 12-17 year old females were around 13 per million adolescents. This is based on 257 cases out of 5 million adolescents that met the definition of myocarditis. 

The study also reports that cardiac risks for vaccinated boys are 4-6 times higher than their risk of hospitalisation from Covid-19. The authors recommend further research and transparency on the benefits and risks of vaccination in children.

The results are based on reports in the US Vaccine Adverse Event Reporting System, which can lead to over-estimates of risks. The authors state that they used the CDC definition for probable myocarditis to identify cases to reduce the risk of over-estimation. The paper has not yet been peer reviewed

Modelling vaccination scenarios

ESR has produced a vaccination modelling application to explore and visualise the implications for different levels and effectiveness of vaccination. This is based on a paper published in The Lancet Regional Health Western Pacific.

Other SMC resources