Vaccine-related papers

Moderna may be slightly more effective than Pfizer’s vaccine

The Moderna vaccine had slightly greater effectiveness when compared with the Pfizer/BioNTech vaccine. Nearly 220,000 matched people were in each vaccine group, and effectiveness was monitored out to 24 weeks after full vaccination.

While infection rates were low in both groups, the Moderna vaccine consistently resulted in lower risks for infections and hospitalisations. The risk of death following infection were similar for both vaccines.

The study period was between January and July, when Alpha mostly dominated infections. But similar results were found for Delta infections.

Several factors (such as mRNA concentration, dose interval, or lipid compositions in the vaccines) may contribute to the difference in effectiveness. The study is based on health records from US Veterans Affairs hospitals, so participants were mostly male and over 50. The paper was published in the New England Journal of Medicine.

While the Pfizer/BioNTech vaccine may have an edge over the AstraZeneca/Oxford vaccine

Neutralising antibody concentrations were significantly higher after two doses of the Pfizer/BioNTech vaccine than after the AstraZeneca/Oxford vaccine.

Serum samples were collected about 14 days after vaccination. Neutralisation activity for both vaccines was about five times lower against the Delta variant than a wildtype strain. Those who received the AstraZeneca vaccine were on average 15 years older than Pfizer recipients, which may have an effect on the results. The paper was published in PLOS Pathogens.

A range of vaccines boost immune responses after two AstraZeneca or Pfizer doses

A randomised controlled Phase 2 trial found that seven vaccines boosted immune responses after two doses of either the AstraZeneca/Oxford or Pfizer/BioNTech vaccines. Antibody levels were increased more after a third dose for those initially vaccinated with the AstraZeneca vaccine than the Pfizer.

The seven vaccines used for third doses were AstraZeneca, Pfizer, Novavax, Moderna, Johnson & Johnson/Janssen, Valneva (an inactivated virus), and CureVac (an mRNA vaccine now withdrawn from clinical development). Some of the vaccines were given as full or half doses.

The third dose was given after at least 70 days (for the AstraZeneca vaccinated participants) or 84 days (for Pfizer), which are shorter intervals than most public health recommendations. The degree of immune boost 28 days after a third dose varied by vaccine combinations. The mRNA vaccines increased antibody responses more than the other vaccines, and the Moderna vaccine boosted T cell levels the most.

Only the Valneva vaccine failed to boost immune response when given after the Pfizer vaccine, although numbers of participants in each group were relatively small (around 100).

While adverse reactions to the third dose varied between combinations, there were no reactions that caused concern. Further research is needed to determine whether a half dose is as effective as a full one for a third dose. It is unknown how much specific increases in antibody levels and neutralisation activity affect protection from infection or serious disease. The paper was published in The Lancet.

In a separate study improved neutralisation of both the Beta and Delta variants was seen when a third vaccine dose was given at least six months after two doses of the Pfizer/BioNTech. This was the case when either the Johnson & Johnson/Janssen or the Pfizer/BioNTech vaccine were the third dose.

Both increased antibody levels to similar levels four weeks after the third dose, while the J&J vaccine increased some T cell levels more than the Pfizer vaccine. The study is based on 65 individuals. The paper has not yet been peer reviewed.

A third vaccine dose can work when the first two don’t

Third mRNA vaccine doses can improve the immune responses in those who had weak responses to two doses. In this study 25% of people produced weak neutralising activity after two doses. Low responses were twice as likely for those receiving the Pfizer/BioNTech vaccine than the Moderna vaccine. When low responders received a third dose (one to eight months after the second) neutralising antibody levels increased by on average 20-fold.

It is not known what level of neutralisation antibodies is required for effective control of infection of Covid-19, but higher levels are assumed to be more effective than lower ones. The authors suggest individual tests of neutralising antibody levels to determine if the person requires a third vaccine dose. The paper has not yet been peer reviewed.

More support for strong immune response after infection plus one vaccine dose

Another study reports strong immune responses after one Pfizer/BioNTech dose in people with earlier infections. The paper was published in Science Translational Medicine.

A longer interval between Pfizer doses can significantly improve immune response

A 16 week gap between the first and second Pfizer/BioNTech doses significantly increases the humoral immune response, compared with a four week interval. Not only were antibody levels significantly increased, but neutralisation of some variants of concern or interest improved as well.

The humoral response following the 16 week interval was similar to that for a previously infected person who had had a single vaccine dose. However, the immune response declined more quickly in uninfected vaccinated people than in those who had a prior infection plus a vaccine. Fifty three participants were in the study. The paper was published in Cell Host & Microbe.

Macaques still have good protection one year after having the Moderna vaccine

Macaques were able to mount a robust response against the Delta variant one year after receiving the Moderna vaccine. While antibody levels declined over time, their binding ability improved. Infection in the lower respiratory tract was controlled, although more slowly than when infection occurred soon after vaccination.

Control of infection in the upper respiratory tract was less effective, probably reflecting the higher levels of antibodies needed for protection in the nose compared with the lungs. The authors suggest a booster dose may help reduce transmission risks and development of severe disease. Infection dynamics in macaques may not be the same as in people. The paper was published in Cell.

Vaccination can reduce the risk of long Covid

Further evidence supports vaccination reducing the risk of developing long Covid. Patients who had had at least one dose of a vaccine (Pfizer/BioNTech, Moderna, or Johnson & Johnson/Janssen) prior to being diagnosed with Covid-19 were 7-10 times less likely to report two or more long Covid symptoms compared to unvaccinated patients.

Reduction in the risk of long Covid can occur even if vaccination occurs after the infection. Unvaccinated patients who received their first vaccination within four weeks of infection were 4-6 times less likely to report multiple long Covid symptoms, and those who received their first dose 4-8 weeks after diagnosis were three times less likely to report multiple long Covid symptoms.

The study is based on the records of over 240,000 patients. Demographic factors and chronic conditions also influence the likelihood that an individual will develop long Covid, but vaccination reduces the risk even when these factors are taken into account. The paper has not yet been peer reviewed.

Vaccinated people who died of Covid-19 had very high viral loads

Autopsies of vaccinated people who died due to Covid-19 found very high viral loads and wider distribution of the virus throughout the body, compared with unvaccinated deceased individuals. Viral loads and distribution were usually greater in partially vaccinated than fully vaccinated cases.

Most of the vaccinated who died were elderly and had several comorbidities, and death was much more common for unvaccinated than vaccinated patients with Covid-19. The paper has not yet been peer reviewed.

‍