Study shows poor antibody response in naive elderly of nursing homes after mRNA vaccination

A new study describes inadequate antibody responses to the Pfizer/BioNTech vaccine against coronavirus disease 2019 (COVID-19) in elderly residents of a care home with no prior history of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), compared to those with such a history. This adds to the current understanding of vaccine efficacy against infection.

The study (not yet peer-reviewed) has been released as a preprint on the medRxiv* server.


Nursing home (NH) residents made up almost a third of all COVID-19-related deaths in the USA, though only 5% of the total cases. This led to their being given top priority during vaccine rollouts in almost every country, and in the US, high coverage of this group has been achieved.

This has gratifyingly reduced the number of cases and of deaths in these homes beyond the fall observed at the national level.

Nonetheless, the success of vaccines based on the messenger ribonucleic acid (mRNA) platform has been found to be surprisingly low in older adults, as well as in adults with type 2 diabetes and cardiovascular conditions. Since these are very common among nursing home residents, the current study was focused on vaccine efficacy in this group.

An earlier Danish study showed that only 64% of NH residents responded adequately to two doses of the Pfizer vs. 90% of healthcare workers.

To add urgency to this study, emerging variants are more resistant to neutralizing antibodies elicited by earlier strains or the wildtype virus. Breakthrough infections have been reported to occur in fully vaccinated healthy adults, while a Kentucky nursing home suffered an unexpected outbreak of severe COVID-19, with some deaths caused by the R.1 variant.

Natural infection seems to protect better against such breakthrough infections, with or without vaccination. However, the vaccine boosts the antibody titers to higher levels in adults with a history of prior SARS-CoV-2 infection. This aspect was also studied in the present study, which compared both naïve and recovered NH residents in terms of cross-reactivity induced by mRNA vaccination.

Antibodies undetectable in naïve subjects

Baseline levels of virus-specific immunoglobulin G (IgG) antibodies were below the limit of detection in uninfected (naïve) staff and residents, but previously infected (PI) individuals in both groups had high antibody levels. One dose of the vaccine caused a marked rise in specific antibodies in both naïve and PI subjects, with a further rise following the second dose.

However, antibody titers to the viral spike and the receptor-binding domain (RBD) were six-fold lower for naïve residents vs. naïve staff. The gap narrowed two-fold after both doses.

S2 antibodies were consistently lower than either S1 or RBD antibodies, especially among naïve individuals.

Neutralizing activity lower in vaccinated residents vs. staff

Neutralizing antibody titers were detectable in almost all naïve staff by day 28, but became undetectable in a quarter of them by the end of week 7 post-vaccination. Conversely, only a quarter of naïve residents developed neutralizing antibodies by day 28, increasing to almost a half by the second time point.

At seven weeks post-vaccination, most PI individuals had neutralizing antibody titers against both the wildtype and the B.1.351 variant. B.1.351 antibody titers were 5-10-fold lower compared to the wildtype virus. Conversely, few naïve individuals developed neutralizing antibodies to this strain following vaccination.

The anti-RBD antibodies elicited by a single dose of the vaccine showed strong avidity for the RBD in both naïve and PI staff, but among residents, only those with prior infection.  

The booster dose induced an increase in avidity only in naïve subjects, but greater in staff compared to residents.

Poor responders among staff and residents

Clustering by antibody levels, antibody avidity and neutralizing activity at day 49 yielded five clusters. These age-independent groups showed a pattern where high antibody responses correlated with a higher proportion of PI individuals.

The cluster with the lowest antibody responses contained naïve subjects, both residents and staff, indicating that some staff were also poor responders to vaccination.

What are the implications?

Overall, considering residents and staff together, binding antibodies against both the spike S1 domain and the RBD were higher in the vaccinated PI group at four weeks post-vaccination.

Neutralizing titers at seven weeks were also higher in the vaccinated PI group. While PI residents had higher binding antibody levels compared to PI staff, reflecting their survival of severe infection, naïve residents had lower titers of neutralizing antibodies than naïve staff, probably due to a weaker immune response to the vaccine.

Thus, PI residents seem to be at low risk of breakthrough infection following vaccination, in view of the prompt and energetic response observed.

The findings suggest that NH residents naïve to SARS-CoV-2 infection had a weaker antibody response to mRNA vaccination compared to staff. This included weaker neutralizing antibody responses as well, with weaker avidity for the RBD. The reason for this appears to be related to frailty rather than age.

None of the naïve NH residents had any detectable humoral immunity to the B.1.351 variant.

The researchers write:

The poor Ab responses observed in our study are therefore likely associated with lower vaccine-induced protection. Providing optimal protection to NH residents [as well as younger poor responders] may require adapted vaccination regimens, such as additional doses of homologous or heterologous vaccines.”

*Important notice

medRxiv 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.

Journal reference:
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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