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COVID Jab Most Effective for Lymphoma Patients After 4 Doses

Research into the effectiveness of COVID-19 vaccination for protecting patients with lymphoma suggested that repeated doses increased protection against SARS-CoV-2, particularly after four doses.

Scientists from the University of Southampton said the findings, from the 2-year Prospective Observational Study Evaluating COVID-19 Vaccine Immune Responses in Lymphoid Cancer (PROSECO) trial, supported the need to promote COVID-19 booster vaccine uptake, particularly among people who were immunocompromised.

The team, from the university's Centre for Cancer Immunology, aimed to evaluate the strength of cancer patients' immune system to the vaccine and how effective it proved in protecting them from COVID-19. They examined the link between antibody levels and T-cell responses with SARS-CoV-2 infection and symptom severity.

18-Month Investigation

The study, published in The Lancet, enrolled 592 participants with lymphoma from nine hospitals in England between March 2021 and September 2022, for longitudinal peripheral blood sampling before and after one to four COVID-19 vaccine doses. Of the participants, 524 were eligible for analysis following vaccination and were asked to complete a follow-up questionnaire to measure infections and their previous social behaviours. Of the 396 who responded to the questionnaire, 334 were eligible for analysis after two vaccine doses, 315 after three vaccine doses, and 266 after four doses.

Investigators reported that 6% of the patients with lymphoma developed a breakthrough infection – defined as a SARS-CoV-2 infection occurring 2 weeks or more after vaccination – following two vaccine doses, 13% after three vaccine doses, and 14% after four doses. However, the researchers hypothesised that the lower infection rate following two vaccine doses might be due to reduced exposure to the virus during national lockdowns and differences in infectivity of the circulating variants.

Breakthrough infection after the second vaccine dose occurred during the alpha (B.1.1.7), delta (B.1.617.2), and omicron (B.1.1.529, BA.1, and BA.2) variant waves, whilst infections following third and fourth vaccine doses occurred mainly during the omicron wave only. Most breakthrough infections occurred after third and fourth doses were administered, coinciding with increased transmissibility characteristic of the omicron variant, they observed.

Higher Quality Antibodies

The researchers found that a fourth vaccine dose generated antibodies that were more effective, compared with those seen following a third dose. They suggested this could be attributable to higher quality antibodies being produced with each successive dose. They also observed that in nine participants who were admitted to hospital with COVID-19, over half (56%) had absent T-cell responses, compared with only a fifth (16%) of 45 participants who were infected but did not require hospital admission.

Dr Sean Lim, an associate professor at the University of Southampton, who led the investigation, commented: "While the threat from COVID-19 is greatly reduced for most of us, for those with weakened immune systems, such as blood cancer patients, the risk remains very real. Our findings support the need for immunocompromised patients to continue booster vaccinations to maintain a high level of protection."

The study also recommended "standardisation and commencement of routine antibody testing in people who are immunocompromised to enable precise risk delineation for individuals, and focusing of efforts to protect the most vulnerable groups".

A new study, Stratification of Clinically Vulnerable People for COVID-19 Risk Using Antibody Testing (STRAVINSKY), plans to investigate whether antibody testing can also identify those who remain at greatest risk of severe COVID-19 infection after vaccination, in vulnerable populations beyond lymphoma patients. The 2-year investigation, led by researchers from Southampton, Birmingham, Oxford, Imperial College and Queen Mary in London, is due to start recruitment shortly.

The PROSECO study is funded by the Blood Cancer UK Vaccine Research Collaborative, which is led by Blood Cancer UK in partnership with Myeloma UK, Anthony Nolan, and the British Society for Haematology, and the British Society for Haematology, awarded to SHL and supported by a Cancer Research UK Advanced Clinician Scientist Fellowship to SHL, Cancer Research UK, and National Institute for Health Research (NIHR) Southampton Experimental Cancer Medicine Centre awarded to AJD, NIHR Southampton Clinical Research Facility Southampton Research Biorepository, and NIHR Southampton Biomedical Research Centre. GPC receives support from the NIHR Oxford Biomedical Research Centre and Cancer Research UK Experimental Cancer Medicines Centre. MJA receives support from NIHR Leicester Biomedical Research Centre.


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