The immune response to SARS-CoV-2 vaccination in older people

The rapid development of vaccines against SARS-CoV-2 infection and their use through mass vaccination campaigns has proved to be a highly successful strategy to reduce the effects of the COVID-19 pandemic. The deployment of SARS-CoV-2 vaccines to older adults at risk of severe disease has been a priority in most countries.1Cadeddu C Rosano A Villani L et al.Planning and organization of the COVID-19 vaccination campaign: an overview of eight European countries.Vaccines (Basel). 2022; 101631 Google Scholar Monitoring of the immune response represents a fundamental complement to vaccination campaigns. Studies so far have shown that although SARS-CoV-2 vaccines are less effective in older individuals,2Wang J Tong Y Li D Li J Li Y The impact of age difference on the efficacy and safety of COVID-19 vaccines: a systematic review and meta-analysis.Front Immunol. 2021; 12758294 Crossref Scopus (26) Google Scholar, 3Fedele G Trentini F Schiavoni I et al.Evaluation of humoral and cellular response to four vaccines against COVID-19 in different age groups: a longitudinal study.Front Immunol. 2022; 131021396 Crossref Scopus (3) Google Scholar a good response is achieved after two-dose primary vaccination.3Fedele G Trentini F Schiavoni I et al.Evaluation of humoral and cellular response to four vaccines against COVID-19 in different age groups: a longitudinal study.Front Immunol. 2022; 131021396 Crossref Scopus (3) Google Scholar, 4Blain H Tuaillon E Gamon L et al.Antibody response after one and two jabs of the BNT162b2 vaccine in nursing home residents: the CONsort-19 study.Allergy. 2022; 77: 271-281Crossref PubMed Scopus (22) Google Scholar A decline over time of vaccine-induced immune response has also been shown, together with the beneficial effect of a third booster dose.5Fedele G Palmieri A Malara A et al.A third dose of mRNA COVID-19 vaccine significantly enhances anti-SARS-CoV-2 spike IgG response in nursing home residents in Italy.J Am Med Dir Assoc. 2022; 23: 1114-1115Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 6Romero-Olmedo AJ Schulz AR Hochstätter S et al.Induction of robust cellular and humoral immunity against SARS-CoV-2 after a third dose of BNT162b2 vaccine in previously unresponsive older adults.Nat Microbiol. 2022; 7: 195-199Crossref PubMed Scopus (21) Google Scholar Most of the studies focused on the immune response induced by SARS-CoV-2 vaccines in frail older adults living in long-term health-care facilities or specific clinical risk groups, such as patients with cancer or on dialysis. Moreover, only a few studies analysed vaccine-induced T-cell responses. T-cell immunity plays a central role in the control of SARS-CoV-2, and increasing evidence supports a potential role in both preventing initial infection and reducing the severity of disease.7Moss P The T cell immune response against SARS-CoV-2.Nat Immunol. 2022; 23: 186-193Crossref PubMed Scopus (355) Google Scholar Data collected so far have highlighted an impaired T-cell response in people older than 80 years compared with younger adults aged 20–53 years after two vaccine doses,6Romero-Olmedo AJ Schulz AR Hochstätter S et al.Induction of robust cellular and humoral immunity against SARS-CoV-2 after a third dose of BNT162b2 vaccine in previously unresponsive older adults.Nat Microbiol. 2022; 7: 195-199Crossref PubMed Scopus (21) Google Scholar and the immune-potentiating effect of a third booster dose in previously less responsive older adults.6Romero-Olmedo AJ Schulz AR Hochstätter S et al.Induction of robust cellular and humoral immunity against SARS-CoV-2 after a third dose of BNT162b2 vaccine in previously unresponsive older adults.Nat Microbiol. 2022; 7: 195-199Crossref PubMed Scopus (21) Google Scholar, 8Schiavoni I Palmieri A Olivetta E et al.T-cell mediated response after primary and booster SARS-CoV-2 messenger RNA vaccination in nursing home residents.J Am Med Dir Assoc. 2023; 24: 140-147.e2Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar Anthony Ravussin and colleagues9Ravussin A Robertson AH Wolf A-S et al.Determinants of humoral and cellular immune responses to three doses of mRNA SARS-CoV-2 vaccines in older adults: a longitudinal cohort study.Lancet Healthy Longev. 2023; 4: e188-e199Google Scholar describe the immune responses to mRNA SARS-CoV-2 vaccines and epidemiological factors affecting these responses in a national Norwegian cohort of adults aged 65–80 years. The accessibility to a longitudinal cohort of more than 4500 senior adults favourably positioned the authors to understand whether functional and clinical factors can affect the response to SARS-CoV-2 vaccination. In fact, poorer evidence is available on the trajectories of immunity induced by vaccines in the general older age population, and further epidemiological data are needed on this vulnerable population, together with the possibility to identify factors influencing vaccine response. Of importance, the confounding effects of SARS-CoV-2 infection on vaccine responses were excluded through close monitoring of participants during the pandemic. Results of the immunological analyses, done on a subgroup of individuals representative of the whole cohort, confirmed good serological and cellular responses after two vaccine doses, responses which were further improved after the third dose, particularly after heterologous boosting. The authors found that both vaccine type and time since vaccination influenced antibody levels after primary vaccination; after three doses, hypertension was associated with decreased antibody levels. Except for hypertension, the authors did not find any associations between immune response to vaccination and chronic condition or frailty index. However, individuals older than 80 years were not included in the study cohort and the percentage of frail individuals was lower than in the Norwegian population of the same age. Vaccine efficacy against emerging variants of concern (VOCs) is an ongoing concern. In their study, Ravussin and colleagues9Ravussin A Robertson AH Wolf A-S et al.Determinants of humoral and cellular immune responses to three doses of mRNA SARS-CoV-2 vaccines in older adults: a longitudinal cohort study.Lancet Healthy Longev. 2023; 4: e188-e199Google Scholar found that vaccine-induced T lymphocytes recognise mutated epitopes from alpha (B.1.1.7), delta (B.1.617.2), and omicron (B.1.1.529 or BA.1) VOCs. This suggests that vaccine-mediated cellular cross-protection against SARS-CoV-2 VOCs in older adults might compensate for evasion of neutralising antibodies by mutated spike proteins. Albeit roughly 30% of the enrolled participants had a breakthrough infection, most of them had very mild illness, supporting a cross-protective role for T-cell immunity. Overall, Ravussin and colleagues provide important information on vaccination in older adults, a population which requires close monitoring and the implementation of effective preventive measures (ie, booster doses). However, further studies are needed for a better understanding of the heterogeneity of the immune response in older adults considering the changing epidemiological picture. The rapid spread of omicron VOCs had prompted the development of new generation bivalent mRNA SARS-CoV-2 vaccines, containing spike antigen from the ancestral Wuhan strain and the BA.1 or the BA.4-5 omicron VOCs. The administration of additional fourth and fifth vaccine boosters to older adults is being implemented in several countries.10European Centre for Disease Prevention and ControlECDC-EMA statement on booster vaccination with Omicron adapted bivalent COVID-19 vaccines. Sept 6, 2022. European Centre for Disease Prevention and Control, Solna2022Google Scholar Monitoring studies are needed to identify how immune responses change with new formulations and additional vaccine doses, and continuously tracing the effects of SARS-CoV-2 vaccination is mandatory. Answering questions on duration of vaccine-induced immunity, on the definition of immunological surrogates of protection from breakthrough infections and severe disease, and on the identification of at-risk patients and vaccine low-responders will bring key support to public health decisions on the definition of future vaccination strategies in the older age. We declare no competing interests. Determinants of humoral and cellular immune responses to three doses of mRNA SARS-CoV-2 vaccines in older adults: a longitudinal cohort studyMost older adults, including those with comorbidities, generated good serological and cellular responses after two vaccine doses. Responses further improved after three doses, particularly after heterologous boosting. Vaccination also generated cross-reactive T cells against variants of concern and seasonal coronaviruses. Frailty was not associated with impaired immune responses, but hypertension might indicate reduced responsiveness to vaccines even after three doses. Individual differences identified through longitudinal sampling enables better prediction of the variability of vaccine responses, which can help guide future policy on the need for subsequent doses and their timing. Full-Text PDF Open Access