mRNA booster vaccination found to protect aged mice against the Omicron variant of SARS-CoV-2

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which harbors numerous mutations at the viral spike protein, evades host immunity by escaping neutralizing antibodies (NAbs) induced by vaccines. This variant promptly became predominant at the end of 2021 and caused stark increases in the rate of infections even among populations who had acquired immunity to SARS-CoV-2.

To combat the emergence of newer variants, booster doses of dose of messenger ribonucleic acid (mRNA) vaccines are being administered, which aid in the generation of neutralizing antibodies in the host. The elderly population faces the greatest risk of severe coronavirus disease 2019 (COVID-19) – induced by SARS-CoV-2 infection. Owing to immunosenescence, the immune responses of older people are relatively weaker.

However, whether a booster vaccination dose can render better protection against Omicron among the elderly and the geriatric populations remain unknown.

The study

A recent study posted on Research Square* aimed at examining the protective effect of the mRNA booster vaccine against the SARS-CoV-2 Omicron variant in extremely aged (21-month-old) mice. Here, multiple immunization regimens of mRNA BNT162b2 vaccine (Pfizer-BioNTech) were evaluated to assess the effect of a booster dose administered eight months post the primary immunization, over the lifespans of murine and in extremely aged mice. 

Findings

This is the first study that demonstrates the effect of booster immunization doses on immunogenicity in a murine model. Even though epidemiologically the Omicron variant seems to induce a milder disease when compared with previous strains, the morbidity and mortality in the elderly remain a major threat—as vaccine-induced immune responses are low in this population. 

Booster COVID-19 vaccination doses were reported to dramatically increase both, humoral and T-cell responses across all age groups. The results showed that in extremely aged mice, a booster dose elicited sterilizing immunity against the Omicron variant, whereas, mice that did not receive a booster dose did not have adequate immunity for viral eradication from the lungs.

On the other hand, younger mice without a booster remained protected from lung infection due to SARS-CoV-2. Furthermore, neutralizing antibodies were found to be closely linked to protection against Omicron. These findings substantiate the efficacy of booster doses and the need for a precise approach for protection in susceptible populations.

While the increasing age was linked to lower humoral immune responses following the first vaccination series, extremely aged mice exhibited a comparable escalation in specific immunoglobulin (IgG) and NAbs against the wild-type SARS-CoV-2 (WT) strain after receiving a booster dose. NAbs were not detected in any of the aged mice against Omicron after eight months following the primary immunization series; these mammals exhibited robust neutralizing activity on receiving a booster dose.

Although NAbs can predict vaccine effectiveness (VE) against the wild-type strain as well as the earlier variants, whether the same was true for the Omicron variant remained unclear. 

Additionally, a booster dose, when administered in extremely aged mice, markedly increased the CD4+ and CD8+ T cell responses targeting the Omicron spike protein, which were comparable to those elicited by younger mice after a booster vaccination dose. Of note, aged mice had earlier shown low levels of T cell responses, eight months post the primary vaccination series

It was worth noting that regardless of the age and vaccination schedules, T cell responses induced by the ancestral spike-specific mRNA vaccine (targeting the ancestral wild-type strain) could identify the Omicron variant. Thus, T cells play a crucial role in immunity against the Omicron variant.

Interestingly, a few mice seemed to remain protected against lung infection despite no detectable neutralizing activity. The findings suggested that both, humoral and cellular immunity are instrumental in protection against Omicron.

Limitations

Although this study accounts for age-specific immunity, as well as humoral and cell-mediated immunity, and performs a live efficacy evaluation of vaccines against SARS-CoV-2, it has its share of limitations.

Firstly, this study only renders animal data. Secondly, owing to the longitudinal study design, some groups had smaller numbers of mice, limiting some statistical comparisons. Thirdly, analysis of viral loads was only done within the lungs since the focus was to study protection against severe lower respiratory infection. The results also failed to address whether a booster dose could suppress or prevent symptomatic infection, asymptomatic infection, and/or subsequent transmission.

Furthermore, similar results related to the upper respiratory tract remain elusive. Lastly, this study assessed acquired immunogenicity against SARS-CoV-2 and the protective efficacy of the booster mRNA vaccination dose at a short timepoint.  

Inference

Eight months after the primary vaccination doses, a marked decrease in vaccine-induced immune response was observed in aged mice. Administration of a booster dose brought about a dramatic increase in antibody and T cell responses – evidenced by cross-recognition of the Omicron variants. Therefore, the results highlight that mRNA booster immunization doses could potentially protect the older populations against the newer variants of SARS-CoV-2.

In addition, the findings emphasized the importance of recognizing age as a critical parameter in the present and future vaccine designs.

*Important notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Nidhi Saha

I am a medical content writer and editor. My interests lie in public health awareness and medical communication. I have worked as a clinical dentist and as a consultant research writer in an Indian medical publishing house. It is my constant endeavor is to update knowledge on newer treatment modalities relating to various medical fields. I have also aided in proofreading and publication of manuscripts in accredited medical journals. I like to sketch, read and listen to music in my leisure time.