Should older people be vaccinated on priority?

Abu Muhammad Zakir Hussain | Published: 00:00, Mar 02,2021


PEOPLE, in general, and decision makers in the health sector, in particular, have to know about the possible and real efficacy of a vaccine to COVID-19 in people older than 65 years of age, so that a confident and informed decision may be taken on vaccinating older people and thereby ensuring an efficient use of the scarcely available resource.


Theoretical background of immunity

‘IMMUNOSENESCENCE’ means a declining strength of developing immunity due to age. The naive T white blood cells, which respond to infection or a vaccine, fall in functionality, survival and in number with age. The ratio of CD4+:CD8+ molecules borne on the T cell surface rises in older age, as CD8+ T cells fall. T cell receptor diversity to fight against different forms of pathogens in both CD8+ and CD4+ cells falls with age. Production of short-lived T cells rather than T cells, which carry memory of a previous infection, is enhanced, which may result in an impaired response of T cells to infection or vaccination. B white blood cell number remains more consistent with age but, due to a reduced production of proteins in old age, fewer functional antibodies are produced by B cells. Vaccines, therefore, may be less effective in older people.

In a recent study published in the journal Perspectives on Psychological Science, investigators demonstrated that depression, loneliness, stress and poor health behaviours can cause the immune system to weaken, ultimately impacting how it would respond to a vaccine. These are more common phenomenon among older people.

The presence of antibody and its concentration may not impart adequate immunity on their own. The risk of serious adverse events mediated by over-activation of the immune system is usually lower among older people, reflecting on a weaker potential of development of a strong immunity among them.


The AstraZeneca vaccine

ASTRAZENECA, as a rebuttal to the German newspaper column Handelsblatt and Bild, which informed their readers that the vaccine is 8–10 per cent efficacious among people older than 65 years, stated that ‘In November, we published data in The Lancet demonstrating that older adults showed strong immune responses to the vaccine, with 100 per cent of older adults generating spike-specific antibodies after the second dose,’. Phase II trial of the AstraZeneca vaccine included 200 people aged 70 or over, without severe comorbidities or frailty. This claim of cent per cent efficacy of the vaccine in older people, however, has to be matched with AstraZeneca’s own claim that their vaccine is in general 70 per cent effective when the two doses of their vaccine are administered eight to twelve weeks apart, a deviation from the four-week gap as per their approved protocol. If the readers remember, AstraZeneca claimed in the beginning that its vaccine is 62 per cent effective but it came up later with two figures — 70 per cent and 90 per cent. About 90 per cent efficacy was obtained when some 2,471 people, in the second phase of the trial, got half of the originally approved dosage by mistake in the UK, in the first shot and 70 per cent is the average of this 90 per cent and the 62 per cent.

The German health ministry, however, also contradicted the source for the 8 per cent figure, but did not comment on the Bild report of lower than 10 per cent efficacy. However, as it stands now, eleven European Union countries are not allowing the vaccine for people older than 65 years. The Lancet paper stated, ‘As older age groups were recruited later than younger age groups (in the third phase trial), the efficacy data in these cohorts are currently limited by the small number of cases.’

Adam Finn, a Professor of Paediatrics at the University of Bristol, gave a very interesting observation. He said, ‘Elderly people were recruited to the UK phase 3 relatively late and were (after vaccination) relatively well shielded (protected from exposure to infection), so there were few cases of COVID-19 that had occurred at the time of submission of data to MHRA for approval.’


Moderna and Lonza vaccine

A PHASE I study of the Moderna vaccine in ‘older adults’ published in the New England Journal of Medicine received considerable media attention as it found an antibody response which was similar irrespective of age. However, the study included only 40 healthy people aged over 58 years, without any mention on how many of them were above 65 years of age. Also, its relevance to frail people was unclear. The number of trial participants, aged 71 years and above, was only 20 (the mean age being 72.6 years, which probably means an upper range not exceeding 75 years of age). Over 25 per cent participants of the Moderna phase III trial were aged 65 years and above and a similar proportion is said to have chronic diseases, ie who are at risk of progression to severe COVID-19, eg those suffering from diabetes, chronic lung disease, severe obesity, significant cardiovascular disease, liver disease, or infection with HIV. The Food and Drug Administration of USA, however, noted a lower efficacy of the vaccine for people above 65 years of age. A total of thirteen deaths were reported in the trial, with two aged over 75 years who had pre-existing cardiac disease.


Pfizer and BioNTech vaccine

‘OVERALL, the sparse data from Phase II trials suggest a reduction in both antibody responses and mild to moderate adverse events in well older people compared to younger participants. Many of the Phase III trials have made a conscious effort to recruit older people, and interim analyses of the Pfizer and Moderna vaccine have led to press releases announcing high degrees of efficacy. However, older people with co-morbidities and frailty and care home residents were once again largely excluded and there are no published data on safety and efficacy in this group’.

A Pfizer press release claimed over 95 per cent efficacy in 65 years and above age group. But they did not reveal any supporting data and suggested that over 40 per cent of the participants in their Phase III trial were aged 56–84, without clarifying what percentage was above 65 years of age. Please note that the median age of their series was only 52 years. Although 21 per cent of them had at least one underlying comorbidity, but what was it, was not mentioned.

The systemic adverse effects of BioNTech vaccine were: fever, fatigue, headache, chills, vomiting, diarrhoea, muscle and joint pain. These reactions were less common and milder in older adults than younger adults (which could mean a poorer development of immunity among older population). Severe reactions (Grade 3) were reported in fewer than 2 per cent of vaccine recipients after either dose. Rates of serious adverse events were similar between vaccine and placebo groups (0.6 per cent and 0.5 per cent) according to the manufacturer. But a number of post-vaccine deaths were reported in USA, Europe and Africa, which were claimed to be unrelated to the vaccine.  


Other vaccines

SPUTNIK-V vaccine was claimed to be 92 per cent effective. The vaccine has been approved in Russia, Belarus, Serbia, Argentina, Bolivia, Algeria, Palestine, Venezuela, Paraguay, Turkmenistan, Hungary and the UAE; and the process to approve the vaccine in the EU has been initiated. The manufacturer claimed that no strong allergies were noticed for Sputnik V. No detail is available however on the Sputnik V vaccine on age or race. Its third phase trial is expected to end in March 2021, before which not much may be known.

Johnson and Johnson, very recently claimed its vaccine to be 85 per cent effective against moderate and severe infection in all ages. It is also claimed to be sensitive to the South African and new USA mutants. Janssen’s phase II trial included just 15 participants aged 65 and over, with lower rates of adverse events (36 per cent) than in younger people (64 per cent). But the details of its protocol have not been publicly released yet, until then the efficacy of the ‘Janssen’ vaccine on the older people and on other mutated forms of the virus will be awaited. The vaccine, on day 14 showed CD4+ T-cell response in 76–83 per cent of the participants aged 18–55 years, but 60–67 per cent in participants above 65 years of age.

Novavax said it will recruit a minimum of 25 per cent of people aged 65 and over; but those aged 85 and over and those with complex comorbidity have been excluded. Phase II trial has reported the result for the younger people only.

China’s vaccines were tested in people less than 60 years of age so far. Phase III trials for Sinopharm’s vaccine, named ‘Vero’ have been conducted in the United Arab Emirates, Bahrain, Peru, Serbia, Morocco, Argentina, Jordan and Pakistan. The UAE and Serbia approved the vaccine. Sinopharm vaccine, in addition to pain in the injection site and headache, includes side effects such as high blood pressure, loss of vision, loss of taste, delayed menstruation and urinary incontinence. Phase III trials in the UAE found that the vaccine had an efficacy rate of 86 per cent in preventing infection (79 per cent efficacy was found in China). The vaccine was claimed 100 per cent effective in preventing moderate to severe cases of COVID-19. Sinovac’s Coronavac vaccine was assessed by the Brazilian collaborators to be 78 per cent effective (after the gap between two doses is about four weeks). Indonesian health authorities reported an efficacy of about 65 per cent, while Turkey reported 91 per cent efficacy of the vaccine.


Some generic thoughts

NEW variants of the SARS-CoV-2 strain in South Africa and Brazil (B.1.1351 and P1 respectively), which have a common point mutation, E484K, are spreading globally. It was also reported by the Gonoshasthaya Kendra in a person living in a rural area in Bangladesh. It appears that the vaccines available in the market right now might not work against these variants. South Africa stopped AstraZeneca vaccine on the same ground. But elsewhere where E484K is not predominant, we have no issue with the vaccine. It should be good enough to create ‘herd immunity’, if every person at risk of infection is vaccinated.   

In the face of vaccine shortage and the possibility of development of poor immunity in the older people, the government needs to prioritise those who are at greater risk of getting infected and infecting others. If they are immune, the disease might not be transmitted to their elderly, who can and mostly stay at home. We also need to keep in mind that since the possibility of getting enough vaccine for all the eligible in the country within 2021 is slim, it will be advisable that only those who are non-immune are vaccinated. This means, those who were infected in the last six months, according to the World Health Organisation, might not be vaccinated for now. France is giving only one jab to the previously infected, taking the infection as the first shot.

The possibility of death, Bell’s palsy, anaphylactic shock etc which have been reported from Norway, Germany, Israel, USA, and India should be kept in mind while approaching the older people for vaccination. Any unpleasant experience in them may discourage other people to get vaccinated. We need to appreciate however, that cost and logistics-wise even the AstraZeneca vaccine is an efficient option for Bangladesh. But we need to develop our own capacity to assess the effectiveness of the vaccine, in terms of both antibody and cellular immunity. This is imperative since many post trial III vaccine rollout findings are being dished out without any peer review, on post-vaccine reduction of transmissibility of the virus and also on different levels of immunity under different conditions.  


Dr Abu Muhammad Zakir Hussain is an epidemiologist and honorary CEO of the Social Sector Management Foundation.  

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