The first wave of the coronavirus disease 2019 (COVID-19) pandemic was associated with significantly higher mortality among older people. As a result, this age group, particularly the vulnerable community living in long-term care facilities or nursing homes, was prioritized in vaccine rollouts in most countries.
However, with the waning of the immune response, it is not clear if these older people respond to the vaccine as well as younger individuals do. A recent study, released as a preprint on the medRxiv* server, explored this question and found that though the antibody levels were somewhat lower in this group, they were still robust. This is a promising observation.
The BNT162b2 (Pfizer–BioNTech) vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the messenger ribonucleic acid (mRNA) platform to deliver instructions to synthesize the viral spike protein within the host cells. This will elicit specific antibodies to guard against future infection.
Clinical trials showed strong neutralizing responses directed against the receptor-binding domain (RBD) of the virus. Cellular responses were skewed towards T-helper 1 (Th1) cells, both CD4+ and CD8+. An overall efficacy of 95% has been reported against symptomatic or severe infection.
Only a few elderly people were included in the trials, however, and the data from phase I trials suggested that the antibody response in this population was weaker relative to younger people. However, cellular responses were not studied.
The researchers used data from about 60 nursing home residents (NHR) with a median age of 88 years. Over 80% of them were seronegative at baseline, even when tested for antibodies binding outside the RBD.
All had received at least one negative test (by reverse transcriptase-polymerase chain reaction, RT PCR) on nasopharyngeal swabs as part of a nursing home screening policy.
Seropositive individuals made up 17% of the study group, and these had a history of positive tests and clinical symptoms. After completion of the two-dose vaccination regimen, 43 of the 49 patients without prior infection history were tested for antibodies.
What was the seroconversion rate?
Most of them (41/43) were antibody positive, when tested for anti-spike antibodies, indicating a seroconversion rate of 95%.
All of them except for one individual tested negative for the viral nucleoprotein (N) antigen. The single N-positive case is thought to have become infected between the first and second doses.
Of the 10 individuals with a history of previous infection, all had antibodies to both S and N antigens when the study began. One died during the vaccination regimen. Of the rest, all showed an increase in antibody levels, with the median increase being 33-fold, though the range varied from a hundred-fold to 600-fold higher.
Thus, the two doses of vaccine acted as a booster in this group, with 94% seroconversion. Notably, both uninfected and infected individuals among NHR showed a high seroconversion response, relative to the controls, with a median age of 49 years.
Of the infection-naïve NHR, the presence of underlying illnesses did not affect the seroconversion rate or the antibody titers.
The blood specimens before vaccination showed that IFN-γ CD8+ T cells specific to SARS-CoV-2 were present in just over a third, and CD4+ T cells in over 60% of naïve NHR.
In the infected subgroup, the corresponding numbers were 60% and 80%, respectively. However, the proportion of both cell responses dropped in all NHRs following vaccination, except for CD8+ T cells in naïve NHR. There was no difference in people with and without chronic illnesses.
In healthy controls, the figures were only about 20% and 30%, respectively. After vaccination, IFN-γ CD4+ T cells and CD8+ T cells were detected in 100% and almost 90% of controls.
What are the implications?
The findings indicate that both NHR and controls showed similar seroconversion rates, above 94%, with comparable antibody levels. The vaccine markedly increased antibody levels in all NHRs with prior infection, relative to naïve subjects, both NHRs and controls.
T cell responses were present in 50% to 70% of NHR, but dropped after vaccination, unlike the increase observed in controls. It is thought that the reactive T cells may have been elicited by seasonal coronavirus infections, which are common in such homes.
It is postulated that some seronegative NHRs might have had asymptomatic infections, but without a detectable antibody response at the time of the study due to waning immunity. This is supported by the report of several outbreaks of the virus in both the nursing homes included in the study.
The controls were drawn from the microbiology laboratory, and may therefore have been infected asymptomatically.
Regardless of the true SARS-CoV-2 infection status of participants, NHR displayed poorer SARS-CoV-2 T-cell responses than healthy controls after vaccination.”
This is discordant from earlier findings of comparable T cell responses following two doses of the vaccine, at all ages, though this may have been influenced by the use of immunosuppression and the presence of underlying illness.
Rather than attributing the weak T cell response to immunosenescence, the researchers suggest that it is necessary to understand whether this is modulated by either cross-reacting cellular responses or SARS-CoV-2-specific T cells. Further work should show how this affects the protective immune response in this case.
An urgent question to be answered relates to whether the decrease in T cells reflects T cell exhaustion by the second dose of the virus, whether these cells are specific or cross-reactive. Some studies suggest that CD4+ T cells to endemic seasonal coronaviruses were reduced in SARS-CoV-2 infection, raising questions about interference with the immune response to the former by the latter.
More work is also essential to understand whether effector T cells with other functionalities take part in the immune reaction to SARS-CoV-2. Overall, the strong antibody responses seen in NHRs are reassuring, but cellular responses show significant variability between controls and NHRs, which requires further examination.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.