As they report in Science, a low dose of the Moderna vaccine lasts for at least six months, and there is no indicator that vaccinated people will need a booster shot.
“This time point is critical because that is when true immune memory has formed,” says LJI Research Assistant Professor Daniela Weiskopf, Ph.D., who co-led the study with LJI Professors Alessandro Sette, Dr.Biol.Sci., and Shane Crotty, Ph.D.
In fact, while the Moderna COVID-19 vaccine (mRNA-1273) led to strong CD4+ (helper) T cell, CD8+ (killer) T cell and antibody responses for at least six months after clinical trial participants were fully vaccinated, it is likely that the immune response could last much longer.
The researchers also show that this strong immune memory lasted in all age groups tested, including in people over age 70, a demographic especially vulnerable to severe COVID-19.
“The immune memory was stable, and that was impressive,” adds Crotty. “That’s a good indicator of the durability of mRNA vaccines.”
Comparing Moderna vaccine to natural immunity
The researchers compared recovered COVID-19 patients to vaccine trial participants who received a 25-microgram dose of the Moderna vaccine during the phase 1 clinical trials (supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health).
“We wanted to see if a quarter of the dose is able to induce any immune response,” says study first author Jose Mateus Triviño, Ph.D., a postdoctoral fellow at LJI. “We had the opportunity to receive the samples from the original Moderna/ NIH phase 1 trial participants who had received two 25-microgram injections of the vaccine, 28 days apart.”
This vaccine dose is a quarter of the 100-microgram Moderna dose given emergency authorization by the Food and Drug Administration (FDA).
While researchers don’t know whether this smaller dose is as effective as the standard dose, this new study shows that the T cell and antibody response in the smaller dose group is still strong.
In fact, the researchers found that the Moderna vaccine spurs an adaptive immune response to the SARS-CoV-2 spike protein (a key target) nearly identical to the immune system’s response to a natural SARS-CoV-2 infection.
“The response is comparable,” says Weiskopf. “It’s not higher and it’s not lower.”
The new study does not show that a lower dose of the Moderna vaccine provides the same protection as the standard dose. “It would take a clinical trial to tell you how protective the lower dose is,” says Crotty.
Common cold viruses do prep the immune system
The new research also shows the power of “cross-reactive” T cells. In a 2020 Science study, the LJI team showed that T cells in people who had recovered from common cold coronaviruses could respond to the novel coronavirus, SARS-CoV-2. At the time, they didn’t know whether this cross-reactivity could actually protect against COVID-19.
“Understanding the role of cross-reactive T cells is important because T cells play an important role in the control and resolution of COVID-19 infections,” says Sette.
For the new study, the researchers found that people with cross-reactive T cells had significantly stronger CD4+ T cell and antibody responses to both doses of the vaccine.
“If you have this immune reactivity, your immune system may kick in faster against the virus,” says Sette. “And multiple studies have shown that how quickly the immune system reacts is key.”
Moderna vaccine activates “killer” T cells
The team also filled in an important gap in COVID-19 vaccine research. Until now, many studies had shown an effective CD4+ T cell response to the Moderna vaccine, but CD8+ T cell data was lacking.
“We know naturally infected and recovered people develop excellent CD8+ T cell responses against SARS-CoV-2; however, there was concern about the generation of CD8+ T cells by mRNA vaccines,” says Mateus Triviño.
The new study shows a strong CD8+ T cell response to the low dose Moderna vaccine, similar to the response after a patient fights a natural SARS-CoV-2 infection, says Sette, a renowned T cell expert.
“We see a robust CD8+ T cell response – and we showed that using multiple assays,” adds Weiskopf.
Will this same vaccine durability hold true for the other types of COVID-19 vaccines? Weiskopf and her colleagues are investigating. In the meantime, Weiskopf says real-world data suggest immune memory does last.
“The people in the hospitals are the ones not vaccinated,” she says.
The researchers are also interested in how the durability of the Moderna vaccine compares with other COVID-19 vaccines in use.
The pandemic of the coronavirus infectious disease 2019 (COVID-19) is continuously evolving, driven by the spread of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During the second half of 2020 and early 2021, a variety of new SARS-CoV-2 variants emerged. EU2 variant (mutation S:447N), first observed in July 2020 in Western Europe, was found to be capable of increasing virus infectivity.1 , 2
Then, several variants of concern (VOCs) have been identified, including B.1.1.7 developed first in the UK in September 2020,3 B.1.351 in South Africa in December 2020,4 P.1 in Brazil in January 2021,5 and the ‘Indian’ variant B.1.617 reported first in Maharashtra in January 2021.6 The disease mortality has been increased in these countries after new variants were developed.7, 8, 9, 10
An increased risk of transmissibility, hospitalization, and death associated with the B.1.1.7 variant was reported by a number of authors.8 , 11, 12, 13, 14, 15, 16 The B.1.351 variant was found to have an increased transmissibility and immune escape17 and was estimated to be 50% more transmissible than pre-existing variants.18
Higher incidence of COVID-19 cases in younger age groups was observed in the Amazonas state, suggesting changes in pathogenicity of the P.1 variant.19 Preliminary findings suggest also a significant increase in case fatality rate in young and middle-aged population for the P.1 mutant.20
The region of Maharashtra, where the B.1.617 variant emerged, experienced a significant rise in daily infection rate after the new variant appeared.10
To control the SARS-CoV-2 spread, a number of different vaccines have been developed and analyzed in clinical trials, including eight vaccines having emergency use or conditional marketing authorizations worldwide or across regions, as of May 2021.21
The worldwide vaccination campaign started in December 2020 aiming to provide herd immunity across societies. The threshold for COVID-19 ‘herd immunity’ was placed between 60 and 70% of the population gaining immunity through vaccinations or past disease exposure; however, scientists warn that herd immunity is unlikely to be achieved owing to factors such as vaccine hesitancy and the spread of new variants.22 , 23
Israel was far ahead of other countries in terms of the proportion of vaccinated inhabitants, exceeding 62% at the end of April 2021, with the UK reaching 50% and the USA 42% at the same time.24
Results of clinical trials on vaccine efficacy revealed that Pfizer-BioNTech had 95% efficacy at preventing symptomatic COVID-19 infection in people without prior infection.25 Efficacy of 94.1% was reported for Moderna,26 70.4% for Oxford-AstraZeneca,27 66.5% for Johnson & Johnson,28 and 96.4% for Novavax,29 with the latter being still under the investigation before authorization.
For the prevention against a severe disease course, Pfizer, Moderna, AstraZeneca, and Novavax reported a 100% efficacy, whereas 84% was observed for Johnson & Johnson; however, the latter was tested on a broader range of countries, including the USA, South Africa, and Brazil, after the new VOCs spread.
Clinical evidence suggests that newly developed virus variants may affect the protective efficacy of both naturally acquired immunity and vaccinations. Studies on neutralization of convalescent sera against distinct strains showed that VOCs were harder to neutralize than the original strain, an early Wuhan-related strain of SARS-CoV-2.
Neutralization titers against the B.1.1.7 variant showed a threefold reduction,30 a 3.4-fold reduction was observed for the P.1 variant,31 and a 13.3-fold reduction for the B.1.531 variant.32 Johnson & Johnson vaccine was found to have 64% efficacy against infection in South Africa and 68% in Brazil after the spread of B.1.135 and P.1 variants, whereas the efficacy against severe-critical disease was 82% and 88% in both countries.28
Late March 2021, AstraZeneca was observed as having 70.4% efficacy against the B.1.1.7 variant;33 however, the vaccine did not protect as well against the B.1.351 variant.34 For Novavax, the initial evidence suggests 86.3% efficacy against the B.1.1.7 variant35 and 49.4% against the B.1.351 variant.36
Early May 2021, Pfizer vaccine was found to be 87% effective against infection with the B.1.1.7 variant and 72% against B.1.351 variant, whereas 97.4% efficacy against severe disease course was observed for any of these mutations.37
On the other hand, Wang et al.38 observed a reduced neutralization of Moderna and Pfizer vaccine-immune sera against the B.1.351 variant (12.4-fold for Moderna; 10.3-fold for Pfizer), but no significant impact was observed for the B.1.1.7 variant.
Next, a 3.8- to 4.8-fold reduced neutralization of Moderna vaccine was observed against the P.1 variant.31 Preliminary evidence suggests a significant drop in neutralization of B.1.617 compared with other variants, including B.1.1.7 and P.1, with sera of Indian’s vaccine, Covaxine.10
The other concern is the probability of reinfection after recovery or vaccination. Hansen et al.39 observed an 80.5% protection against reinfection in a population-level observational study on Danish patients previously tested positive for SARS-CoV-2; however, the study was performed before VOCs spread.
The probability of reinfection after vaccination is also a big concern. As reported by the US Centers for Disease Control and Prevention (CDC), there were around 9200 infections among vaccinated inhabitants among 95 million of those who have already been vaccinated in the USA (0.01%) as of 26 April 2021.40
Despite these optimistic preliminary data, experts alarm that additional data are needed to assess the potential impact of VOCs on future vaccine efficacy.41 Considering all the concerns associated with new VOC spread, the real vaccination effectiveness becomes hard to assess and judge but can be expected to decrease over time.
Also, it is likely that vaccination may favor the emergence of new variants by selection of new, better fitted mutants. Some scientists suggest that, similarly as for seasonal flu vaccines, COVID-19 vaccines will need to be redesigned or even updated periodically to protect against new variants.42 , 43
Vaccination efficacy and distinct variants spread are the only two factors among numerous other variables affecting COVID-19 infection and death rates across the world. A variety of potential predictors were assessed in the literature, including demographic characteristics, mobility and social-distancing measures, environmental and climate variables, as well as health characteristics.44, 45, 46, 47, 48, 49, 50, 51, 52, 53
This study aims at estimating the real-life impact of vaccination on COVID-19 mortality based on publicly available data from Europe and Israel, using time series analysis with non-linear mixed regression models. Variants frequency, including B.1.1.7 and other variants, as well as country-specific demographic and meteorological characteristics, health indicators, and mobility factors were considered as potentially relevant adjustment factors.
Results of the current study should inform policy decision-makers, scientists, and the general public about the role of vaccination and social-distancing strategies in controlling the COVID-19 pandemic in the face of new VOCs spread.
reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413007/
More information: Jose Mateus et al, Low-dose mRNA-1273 COVID-19 vaccine generates durable memory enhanced by cross-reactive T cells, Science (2021). DOI: 10.1126/science.abj9853