In a recent study published in npj Vaccines, researchers reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.5 bivalent booster dose enhanced neutralization of Omicron XBB (sub)variants in non-small cell lung cancer (NSCLC) patients.

Study: BA.5 bivalent booster vaccination enhances neutralization of XBB.1.5, XBB.1.16 and XBB.1.9 variants in patients with lung cancer. Image Credit: Steve Heap/Shutterstock.comStudy: BA.5 bivalent booster vaccination enhances neutralization of XBB.1.5, XBB.1.16 and XBB.1.9 variants in patients with lung cancer. Image Credit: Steve Heap/Shutterstock.com

Background

Monovalent vaccines based on the wild-type SARS-CoV-2 spike messenger ribonucleic acid (mRNA) have been safe and effective against severe disease in most patients with solid tumors.

Nevertheless, SARS-CoV-2 Omicron variants have acquired mutations in the spike protein’s receptor-binding domain, which enable evasion from neutralizing antibodies (nAbs) elicited by vaccines based on the wild-type strain.

Some studies suggest NSCLC patients have poor immune responses to monovalent vaccines and do not develop nAbs against SARS-CoV-2 variants of concern (VOCs).

The study and findings

In the present study, researchers evaluated nAb responses against the wild-type SARS-CoV-2 strain and Omicron variants in NSCLC patients. They obtained plasma samples from 34 NSCLC patients and 12 healthy controls to determine nAb titers against the wild-type strain and BA.5, XBB.1.16, XBB.1.5, BQ.1.1, and XBB.1.9 variants.

Patients in the monovalent booster cohort were double-vaccinated and received the monovalent booster (third dose) six to eight months after the last dose.

NSCLC patients and healthy subjects in the bivalent booster cohort previously received three (monovalent) vaccines and the bivalent booster (fourth dose) 10–12 months after the last dose.

Individuals in the monovalent booster cohort had detectable nAb titers against wild-type SARS-CoV-2, whereas the response was significantly reduced against Omicron variants 40 days after receiving the booster. Specifically, 9% and 18% of the monovalent booster cohort had nAb responses against Omicron XBB.1.9 and XBB.1.16 variants, respectively.

Notably, NSCLC patients receiving the bivalent booster developed a significantly elevated nAb response. All patients in the bivalent booster cohort elicited nAb responses against the wild-type strain and the BA.5 variant.

Further, 65% of patients in the bivalent booster cohort had detectable nAbs to XBB.1.9 and XBB.1.16, and 80% showed responses against XBB.1.5 and BQ.1.1 variants.

Nevertheless, nAb titers against XBB.1.9, XBB.1.5, and BQ.1.1 variants were significantly lower than against the wild-type strain. All healthy individuals in the bivalent booster cohort showed nAb titers against wild-type SARS-CoV-2 and the BA.5 variant.

Moreover, 92% of healthy individuals had nAbs against XBB.1.5 and BQ.1.1 variants, while 83% induced nAbs against XBB.1.9 and XBB.1.16.

Like NSCLC patients, healthy individuals had a significantly reduced nAb response against currently dominant XBB (sub)variants relative to the wild-type virus. Notably, there were no significant differences in nAb titers between healthy participants and NSCLC patients after receiving the bivalent booster.

The team observed a decline in nAb titers against the wild-type strain and Omicron variants among healthy subjects four to six months after bivalent booster vaccination.

Specifically, only 42% of healthy subjects had nAbs against XBB.1.9 and XBB.1.16 variants, and 55% induced nAbs against XBB.1.5. Further, the decline in nAb titers was more prominent in NSCLC patients.

Although nAb titers between NSCLC patients and healthy individuals were not significantly different 40 days post-bivalent booster vaccination, nAb titers to XBB.1.9 and BQ.1.1 variants were reduced among patients four to six months post-boost.

Only 13% and 27% of bivalent vaccine-boosted NSCLC patients had nAb titers against XBB.1.16 and XBB.1.5 variants, respectively, and none of the patients induced nAbs against XBB.1.9.

Finally, the team assessed whether patient demographics and cancer treatment modalities influenced the findings. Age, sex, cancer stage, vaccine type, and race were not statistically different between cohorts.

Patients were categorized based on cancer therapy (immunotherapy, targeted therapy, chemotherapy, and combined therapy). The type of cancer treatment did not influence nAb responses to vaccination.

Conclusions

The study evaluated antibody responses against wild-type SARS-CoV-2 and Omicron variants in NSCLC patients relative to healthy participants after booster vaccination. The researchers observed that only 9% to 27% of patients had nAb titers against XBB (sub)variants following monovalent booster vaccination.

This raises concerns about higher risk of infection among monovalent booster recipients, given that XBB (sub)variants are currently predominant in the United States.

On the other hand, nAb responses against XBB (sub)variants among bivalent vaccine-boosted NSCLC patients were significantly higher and comparable to those in healthy individuals.

Nevertheless, nAb titers declined significantly four to six months post-bivalent vaccination. Cancer treatment type did not appear to influence nAb responses.

The study’s limitations include the relatively small cohort size and single-center recruitment. Also, bivalent cohort subjects received an additional vaccine dose relative to monovalent booster recipients.

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