Neutralization breadth of SARS-CoV-2 viral variants following primary series and booster SARS-CoV-2 vaccines in patients with cancer

Abstract

Patients with cancer are more likely to have impaired immune responses to SARS-CoV-2 vaccines. We study the breadth of responses against SARS-CoV-2 variants after primary vaccination in 178 patients with a variety of tumor types and after booster doses in a subset. Neutralization of alpha, beta, gamma, and delta SARS-CoV-2 variants is impaired relative to wildtype, regardless of vaccine type. Regardless of viral variant, mRNA1273 is the most immunogenic, followed by BNT162b2, and then Ad26.COV2.S. Neutralization of more variants (breadth) is associated with a greater magnitude of wildtype neutralization, and increases with time since vaccination; advancing age associates with a lower breadth. The concentrations of anti-spike protein antibody are a good surrogate for breadth (positive predictive value of =90% at >1,000 U/mL). Booster SARS-CoV-2 vaccines confer enhanced breadth. These data suggest that achieving a high antibody titer is desirable to achieve broad neutralization; a single booster dose with the current vaccines increases the breadth of responses against variants.

Vaccination against SARS-CoV-2 protects from morbidity, mortality and sequelae from COVID19 in patients with cancer

“…These findings may also be related with the emergence of new variants of concern, such as the B.1.617.2 (delta), which has a higher transmissibility than previous strains and proved to cause a higher rate of breakthrough infections 30 , 31 . Taken together, these results support the need of prioritizing frail patients for booster doses, to sustain vaccines immunogenicity over time 32 .…”

Boosting with Omicron-matched or historical mRNA vaccines increases neutralizing antibody responses and protection against B.1.1.529 infection in mice

“…Boosting with historical vaccines, variant-matched mRNA vaccines (Choi et al, 2021; Ying et al, 2021) or possibly heterologous platforms targeting historical spike proteins ( e.g. , adenoviral vectored or protein subunit vaccines (Atmar et al, 2022)) could minimize B.1.1.529 breakthrough infections by increasing the magnitude of neutralizing anti-SARS-CoV-2 antibodies (Atmar et al, 2021; Munro et al, 2021) or expanding the breadth of the antibody repertoire to better control variant strains (Falsey et al, 2021; Naranbhai et al, 2022; Wang et al, 2021). While our data suggest that certain cohorts (those with lower starting antibody responses) might benefit more from an Omicron-matched vaccine, further studies evaluating the magnitude and durability of the boosted immune responses are needed, especially in key vulnerable populations including the elderly, immunocompromised and immunosuppressed.…”

COVID-19 vaccines in patients with cancer: immunogenicity, efficacy and safety

“…For example, 56% of these patients had detectable antibody titres with neutralizing activity against the ancestral Wuhan strain, whereas only 31% had detectable titres with activity against the Delta variant after two vaccine doses 65 . Importantly, the percentage of patients with detectable neutralizing responses to VOCs is broadened following booster vaccination 115 . Initial data on Omicron neutralization in patients with cancer confirm the expected findings deduced from the general population 116 : the percentage of patients with solid tumours with neutralizing responses against Omicron increased from 47.8% to 88.9% following a third vaccine dose 117 .…”

“…Neutralizing antibody responses, which have been investigated only in limited numbers of patients with cancer, can also be boosted using the same vaccine that was initially administered, even in patients lacking a detectable response after the second dose 101 , 147 . Booster vaccination is also associated with an increased ability to neutralize VOCs 115 . T cell responses to booster vaccination have also only rarely been analysed, and the available data indicate no significant increase 101 , a relevant increase only after booster vaccination with an mRNA vaccine 142 and discordant effects in patients who remain seronegative after booster vaccination 144 .…”