Does frequently updating COVID-19 vaccines have any benefits? | Explained – The Hindu
                            February 15, 2024
                                Researchers update the composition of influenza vaccines    every six monthsto match the strains    of the virus that are circulating in the wild, so that the    shots may provide protective immunity against the flu. But    despite their best efforts, researchers rarely perfectly match    the strains loaded in the vaccine with the strains circulating    by the time the vaccines reach the market.  
    The reason for this is the long gestation period  usually at    least six months  between identifying the circulating strain    and the development, manufacturing, and distribution of the    vaccines. By the time the updated flu vaccine is available, the    circulating strain may have drifted from the one contained in the    vaccine, thanks to the high mutational rates of influenza    viruses.  
    The match between strains included in the vaccine and strains    in circulation is the most important factor controlling the    vaccine effectiveness (VE) of flu vaccines. The VE increases    by more than 25%when there is a match    with the circulating strains but can be as low as 10% in    seasons when there is no match.  
    Another issue with flu vaccines is the durability of    protection. According to a recent study, the VE declines by    7% for H3N2 to 11% for H1N1 viruses per    month, and could vanish as soon as90 days after vaccination.  
    There are some striking similarities between the influenza and    COVID-19 vaccines. The VE of COVID-19 vaccines varies according    to the diseases progression as well as the circulating    strains. With the advent of the highly mutated Omicron variant    of SARS-CoV-2, the VE of COVID-19 vaccines has nose-dived.  
    According to one large study, COVID-19 vaccines had a VE of    52.8% against the Delta variant but only 16.4% against the    Omicron. Another large review  of the findings of 78 studies    on the VE of four COVID-19 vaccines before the advent of    Omicron  concluded that VE against symptomatic disease waned    by 20-30% by the sixth month of the primary series.  
    Thus, researchers worldwide rushed to revise COVID-19 vaccines    that contained the ancestral strain to match the circulating    strain of SARS-CoV-2 and keep it clinically relevant.  
    In early 2023, a highly mutated sub-lineage of the Omicron    variant, XBB.1.5, emerged. It was antigenically as distant    from the ancestral strain of SARS-CoV-2 as the latter was    from the SARS-CoV-1 virus. There were three COVID-19 vaccines    available as booster doses at this time: the monovalent    ancestral (OG) shot, a bivalent OG+BA.1 shot, and a bivalent    OG+BA.5 booster. However, as stated above, none of the vaccines    (including mRNA vaccines) were found to be efficacious    against infections of this hypermutated variant.  
    Subsequently, the vaccine was updated in mid-2023 to include    the antigens of the XBB.1.5 strain. But by the time the U.S.    Centers for Disease Control (CDC) approvedand recommended the updated    monovalent vaccine as a booster, another new lineage of    Omicron,JN.1, had emerged with more than 30 mutations in    the spike protein and a high immune-evasion potential. By    January 2024, JN.1 had completely replaced XBB.1.5 in the    population.  
    The CDC estimated the updated booster was around 50%    efficacious against symptomatic JN.1 infections but some    experts doubted this figure.  
    The matching problem raises a pertinent question: Is it prudent    to attempt frequent updates?  
    One interesting study from Australia, uploaded    as a preprint paper on February 9, analysed this question in    detail. Researchers retrospectively analysed 18 studies that    investigated the ability of the OG, the OG+BA.1, and the    OG+BA.5 boosters to neutralise the variant that started    circulating immediately after their deployment. They found that    updated vaccines consistently improved neutralising antibody    titres by 40% or more compared to non-updated vaccine    formulations.  
    Specifically, the researchers found that relative to the OG    antigens efficacy against XBB.1.5, the BA.1 update did a    better job and the BA.5 update did even better. Based on these    benefits in the neutralisation titres, they predicted that    updating an existing vaccine should, on average, induce a    1.52-times higher titre against a future variant compared to    boosting with an older formulation. The researchers also stated    they expect a 11-25% increase in VE against symptomatic disease    and 23-33% against severe disease caused by the future variant.  
    In sum, the study supports the case for revising COVID-19    vaccines formulations as often as possible.  
    However, there are some confounding factors, including past    exposure to infections, inter-study variations of such    exposures, in vitro and in vivo differences, and    publication biases. The researchers also clarified the benefits    of the update would depend on the distance between the    antigens in the updated vaccine and the future variant that    eventually circulates. Indeed, there is no guarantee that a    profoundly drifted variant with a very high transmissibility    and more virulence wont emerge in future, and which would    negate the advantage of updating existing vaccines.  
    Further, the researchers only explored one arm of the immune    system: the humoral immunity conferred by antibodies. The other    arm, cellular immunity conferred by T-cells, wasnt considered.    T-cells are like airbags: they deploy on their own and become    safer to use with every accident (or exposure) that engineers    study. Antibodies are like brakes. Our brain deploys them. They    are terrific when new but suffer wear over time, and need to be    updated.  
    In India, the advent of Omicron (mainly BA.2) in January 2022    and its resultant mild disease rendered a much lower uptake of    COVID-19 vaccines. For many Indians, the pandemic is long past,    notwithstanding a few surges in 2023. Currently, there is no    Indian vaccine with antigens matching the currently dominant    JN.1 strain or its predecessor, XBB.1.5. Corbevax, the vaccine    made by Biological E, is currently developing an XBB-based    vaccine.  
    Whether Indians should be boosted with an updated COVID-19    vaccine depends on the objective. If it is to prevent severe    disease, hospitalisation, and death, only three exposures     through natural infection or vaccination  will suffice to    confer protection irrespective of the antigenic makeup of the    circulating variant. (This protection is provided by our    T-cells.) This is the case with most healthy, immunocompetent    individuals.  
    For the vulnerable sections of society, like the elderly and    those with comorbidities and immunodeficiencies, it is    desirable to actively prevent an infection. These individuals    need an updated booster. The vaccines based on OG or older    strains may not offer meaningful protection owing to the    mismatch and other factors.  
    All available influenza vaccines are being developed on    conventional egg-based or cell-culture platforms, which is why    updating them takes six months or more. Many COVID-19 vaccines    use the mRNA platform whose main attraction is the ease and    speed with which they can be modified. Unfortunately,    updating mRNA vaccines has also required four to six    months.  
    India also has a next-generation mRNA vaccine called Gemcovac, developed    indigenously by Gennova Lab and based on the old Omicron    variant. It can also be updated to use a contemporaneous    variant, but that depends on the need and the will of the    national recommending authority as much as the still-evolving    SARS-CoV-2 virus.  
    Vipin M. Vashishtha is past national convener, IAP Committee    on Immunisation, and director, Mangla Hospital & Research    Center, Bijnor.  
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Does frequently updating COVID-19 vaccines have any benefits? | Explained - The Hindu